As filed with the Securities and Exchange Commission on October 7, 20156, 2021

Registration No. 333-                    

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM S-3

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

DELCATH SYSTEMS, INC.

(Exact Name ofOf Registrant asAs Specified inIn Its Charter)

1301 Avenue of the Americas

43rd Floor1633 Broadway, Suite 22C

New York, New York 10019

(212) 489-2100

(Address, Including Zip Code,including zip code, and Telephone Number, Including Area Code,telephone number, including area code, of Registrant’s Principal Executive Offices)registrant’s principal executive offices)

Jennifer K. Simpson

President andGerard Michel

Chief Executive Officer

Delcath Systems, Inc.

1301 Avenue of the Americas

43rd Floor1633 Broadway, Suite 22C

New York, New York 10019

(212) 489-2100

(Name, Address, Including Zip Code,address, including zip code, and Telephone Number, Including Area Code,telephone number, including area code, of Agentagent for Service)service)

CopiesCopy to:

Steven A. NavarroVeronica Montagna, Esq.

Finnbarr D. Murphy

Morgan, LewisMcCarter & BockiusEnglish, LLP

101 Park Avenue100 Mulberry Street, Four Gateway Center

Newark, New York, NY 10178Jersey 07102

(212) 309-6000(973) 639-7948

Approximate date of commencement of proposed sale to the public:public: From time to time after the effective date of this Registration Statement.registration statement as determined by the selling securityholders.

If the only securities being registered on this Form are being offered pursuant to dividend or interest reinvestment plans, please check the following box.  ¨☐

If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, other than securities offered only in connection with dividend or interest reinvestment plans, check the following box.  x☒

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, please check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ¨☐

If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ¨☐

If this Form is a registration statement pursuant to General Instruction I.D. or a post-effective amendment thereto that shall become effective upon filing with the Commission pursuant to Rule 462(e) under the Securities Act, check the following box.  ¨☐

If this Form is a post-effective amendment to a registration statement filed pursuant to General Instruction I.D. filed to register additional securities or additional classes of securities pursuant to Rule 413(b) under the Securities Act, check the following box.   ¨☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company, or emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer”filer,” “smaller reporting company,” and “smaller reporting“emerging growth company” in Rule 12b-2 under of the Securities Exchange Act of 1934:Act.

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act.  ☐

CALCULATION OF REGISTRATION FEE

The registrant hereby amends this registration statementRegistration Statement on such date or dates as may be necessary to delay its effective date until the registrant shall file a further amendment which specifically states that this registration statementRegistration Statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933 or until the registration statementRegistration Statement shall become effective on such date as the Securities and Exchange Commission, acting pursuant to said Section 8(a), may determine.

The information in this prospectus is not complete and may be changed. We may not sellA registration statement relating to these securities until the registration statementhas been filed with the Securities and Exchange CommissionCommission. These securities may not be sold until the registration statement is effective. This prospectus is not an offer to sell these securities, and iswe are not soliciting an offeroffers to buy these securities, in any state or other jurisdiction where the offer or sale is not permitted.

SUBJECT TO COMPLETION, PRELIMINARY PROSPECTUS DATED OCTOBER 6, 2021

Subject

Up to Completion, Dated October 7, 2015

$77,406,789

DELCATH SYSTEMS, INC.

638,199 Shares of Common Stock

Preferred Stock

Warrants

Debt Securities

Stock Purchase Contracts Offered by the Selling Stockholders

Delcath Systems, Inc. (the “Company”) may offer to sell from time to time common stock, preferred stock, warrants, debt securities and stock purchase contracts. The preferred stock of the Company may be convertible into common stock or preferred stock of another series.

The Company may offer securities at an aggregate offering price of up to $77,406,789. The common stock, preferred stock, warrants, debt securities and stock purchase contracts of the Company may be offered separately or together, in multiple series, in amounts, at prices and on terms that will be set forth in one or more prospectus supplements to this prospectus.

This prospectus describes some ofrelates to the general terms that may apply to these securitiesoffer and the general manner in which they may be offered. Each time the Company sells securities, a prospectus supplement will be provided that will contain specific information about the terms of any securities offered and the specific manner in which the securities will be offered. The prospectus supplement will also contain information, where appropriate, about material United States federal income tax consequences relating to, and any listing on a securities exchange of, the securities covered by the prospectus supplement. The prospectus supplement may add to, update or change the information in this prospectus. You should read this prospectus and any prospectus supplement carefully before you invest in our securities. This prospectus may not be used to sell securities unless accompanied by a prospectus supplement.

The Company may offer the securities directly to investors, through agents designatedresale, from time to time, by the Company,selling stockholders named under the heading “Selling Stockholders” in this prospectus, or their assigns (the “Selling Stockholders”), of up to an aggregate of 638,199 shares of our common stock, par value $0.01 per share (“Common Stock”), consisting of (a) up to 237,614 shares of Common Stock that may be issued to Selling Stockholders upon the conversion of up to an aggregate of 2,376.14 shares of our Series E Convertible Preferred Stock, par value $0.01 per share (the “Series E Preferred Stock”), at a conversion price of $1,198 per share, following an election by such Selling Stockholders to convert the principal amount of, and all interest accruing under, 8% senior secured promissory notes issued by us to such Selling Stockholders (the principal of which is $2 million and accrued interest of up to $846,667 which as of October 5, 2021 is $344,556) into shares of Series E Preferred Stock, (b) up to an aggregate of 378,172 shares of Common Stock that may be issued to a Selling Stockholder, consisting of (i) 250,417 shares of Common Stock that may be issued to such Selling Stockholder upon the conversion of up to $3 million principal amount of a loan made to us by such Selling Stockholder (the “Loan”) and (ii) 127,755 shares of Common Stock that may be issued to such Selling Stockholder upon the exercise of a warrant for 127,755 shares of our Common Stock issued to such Selling Stockholder in connection with the Loan at an exercise price of $0.01 per share (the “Warrant”), and (c) 22,413 shares of Common Stock held by Selling Stockholders, all as described in greater detail under the heading “The Offering” in this prospectus.

Our registration of shares of Common Stock covered by this prospectus does not mean that the Selling Stockholders will offer or through underwriterssell any such shares. The Selling Stockholders may sell shares of Common Stock covered by this prospectus in a number of different ways and at varying prices. For additional information on the possible methods of sale that may be used by the Selling Stockholders, you should refer to the section of this prospectus entitled “Plan of Distribution.” The Selling Stockholders may, individually but not severally, be deemed to be an “underwriter” within the meaning of the Securities Act of 1933, as amended (the “Securities Act”), of the shares of Common Stock that they are offering pursuant to this prospectus. The Selling Stockholders will bear all commissions and discounts, if any, attributable to their respective sales of Common Stock hereunder. We will bear all costs, expenses and fees in connection with the registration of the Common Stock. We will not be paying any underwriting discounts or dealers. If any agents, underwriters, or dealers are involvedcommissions in the sale ofthis offering.

We will not receive any of the securities, their names,proceeds from the shares of Common Stock sold by the Selling Stockholders hereunder. However, assuming (i) the conversion of all of the Series E Preferred Stock following an election to convert the principal amount and all accrued interest under the 8% senior secured promissory notes into such shares, (ii) the conversion of the entire convertible portion of the Loan and (iii) the exercise of the Warrant, we will receive, upon issuance of the Common Stock to the Selling Stockholders $1,278 upon exercise of the Warrant, the outstanding principal amount of the Loan will be reduced by $3 million and the 8% senior secured promissory notes will no longer be outstanding. See “The Offering” and “Use of Proceeds” for more details.

A prospectus supplement may add, update, or change information contained in this prospectus. You should carefully read this prospectus, any applicable prospectus supplement, and the information incorporated by reference in this prospectus and any applicable purchase price, fee, commission or discount arrangement with, between or among them will be set forth, or will be calculable from the information set forth, in an accompanying prospectus supplement. For more detailed information, see “Plan of Distribution.”supplement before you make your investment decision.

Our common stockCommon Stock is traded on theThe NASDAQ Capital Market under the symbol “DCTH.” On October 1, 2015,4, 2021, the lastclosing price for our Common Stock, as reported sale price of our common stock on theThe NASDAQ Capital Market, was $0.43. The aggregate market value$9.58 per share. Our principal executive offices are located at 1633 Broadway, Suite 22C, New York, New York 10019.

Investing in our Common Stock involves a high degree of risk. You should read carefully the outstanding shares of our common stock held by non-affiliates was $9,154,630, basedrisks and uncertainties that are described in (i) the “Risk Factors” section beginning on 21,763,864 shares of common stock outstanding, of which 474,027 are held by affiliates, and a closing sale price on the NASDAQ Capital Market of $0.43 on October 1, 2015. Pursuant to General Section I.B.6. of Form S-3, in no event will we sell securities in a public primary offering with a value exceeding more than one-third of our “public float” (the market value of our common stock held by our non-affiliates) in any 12-month period so long as our public float remains below $75,000,000. We have sold 2,718,878 shares of our common stock and warrants to purchase 1,107,000 shares of our common stock pursuant to General Instruction I.B.6. of Form S-3 during the twelve calendar months prior to and including the datepage 12 of this prospectus.

An investment in our securities involves risks. Seeprospectus, (ii) the “Risk Factors” section of any applicable prospectus supplement or amendment, and (iii) under the “Risk Factors” or similar headings in our latest Annual Report on Form 10-Kperiodic reports and other documents filed with the Securities and Exchange Commission which we refer to as the “SEC,” and any updates to those risk factors or new risk factors contained in our subsequent Quarterly Reports on Form 10-Q and Current Reports onForm 8-K filed with the SEC, all of which we incorporate(the “SEC”) that are incorporated by reference herein.into this prospectus.

Neither the Securities and Exchange CommissionSEC nor any state securities commission has approved or disapproved of these securities or determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense.

The date of this prospectus is        , 2015.2021.

TABLE OF CONTENTS

i

ABOUT THIS PROSPECTUS

This prospectus relates to the offer and resale, from time to time, by the selling stockholders named under the heading “Selling Stockholders” in this prospectus, or their assigns (the “Selling Stockholders”), of up to an aggregate of 638,199 shares of our common stock, par value $0.01 per share (“Common Stock”), consisting of (a) up to 237,614 shares of Common Stock that may be issued to Selling Stockholders upon the conversion of up to an aggregate of 2,376.14 shares of our Series E Convertible Preferred Stock, par value $0.01 per share (the “Series E Preferred Stock”), at a conversion price of $1,198 per share, following an election by such Selling Stockholders to convert the principal amount of, and all interest accruing under, 8% senior secured promissory notes issued by us to such Selling Stockholders (the principal of which is $2 million, and the accrued interest on which as of October 5, 2021 is $344,556) into shares of Series E Preferred Stock, (b) up to an aggregate of 378,172 shares of Common Stock that may be issued to a Selling Stockholder, consisting of (i) 250,417 shares of Common Stock that may be issued to such Selling Stockholder upon the conversion of up to $3 million principal amount of a loan made to us by such Selling Stockholder (the “Loan”) and (ii) 127,755 shares of Common Stock that may be issued to Such Selling Stockholder upon the exercise of a warrant for 127,755 shares of our Common Stock issued to such Selling Stockholder in connection with the Loan at an exercise price of $0.01 per share (the “Warrant”), and (c) 22,413 shares of Common Stock held by Selling Stockholders, all as described in greater detail under the heading “The Offering” in this prospectus.

We will not receive any of the proceeds from the shares of Common Stock sold by the Selling Stockholders hereunder. However, assuming (i) the conversion of all of the Series E Preferred Stock following an election to convert the principal amount and all accrued interest under the 8% senior secured promissory notes into such shares, (ii) the conversion of the entire convertible portion of the Loan and (iii) the exercise of the Warrant, we will receive, upon issuance of the Common Stock to the Selling Stockholders $1,278 upon exercise of the Warrant, the outstanding principal amount of the Loan will be reduced by $3 million and the 8% senior secured promissory notes will be no longer be outstanding. See “The Offering” and “Use of Proceeds” for more details.

This prospectus is part of a registration statement on Form S-3that we have filed with the Securities and Exchange Commission, or the SEC, using a “shelf”shelf registration process. Under this shelf process, weregistration statement, the Selling Stockholders may sell any combination of the securities described in this prospectusCommon Stock from time to time in one or more offerings updescribed in this prospectus. This prospectus omits some of the information contained in the registration statement, and reference is made to a total aggregate dollar amount of $77,406,789. the full registration statement for further information with regard to us, the Selling Stockholders and the securities being offered by the Selling Stockholders.

This prospectus provides you with a general description of the securities we may offer.our Common Stock as well as other information you should know before investing in our Common Stock. Each time wethe Selling Stockholders offer and sell securities,our Common Stock hereby, we will provide aone or more prospectus supplementsupplements or amendments that will contain specific information about the terms of that offering.specific offering of our Common Stock and the specific manner in which it may be offered. The prospectus supplement or amendment may also add to, update or change any of the information contained in this prospectus. To the extent that any statement we make in a prospectus supplement or amendment is inconsistent with statements made in this prospectus, the statements made in this prospectus will be deemed modified or superseded by those made in the prospectus supplement or amendment. You should read both this prospectus and anythe applicable prospectus supplement or amendment together with the additional information described under the headings “Where You Can Find More Information” and Incorporation of Certain Information by Reference” before making an investment decision. This prospectus may not be used to sell our Common Stock unless it is accompanied by a prospectus supplement, or this prospectus is otherwise updated by documents incorporated by reference.

This prospectus contains summaries of certain provisions contained in some of the documents described herein, but reference is made to the actual documents for complete information. All of the summaries are qualified in their entirety by the actual documents. Copies of some of the documents referred to herein have been filed or will be filed or incorporated by reference as exhibits to the registration statement of which this prospectus forms a

part, and you may obtain copies of those documents as described below under the heading “Where You Can Find Additional Information.More Information and Incorporation of Certain Information by Reference.” We urge you to read that registration statement in its entirety, including all amendments, exhibits, schedules and supplements to that registration statement.

You should rely only on the information containedAs used in this prospectus, “Delcath,” “the Company,” “we,” “our,” or “us” mean Delcath Systems, Inc. and its wholly owned subsidiaries. The term “Selling Stockholders” refers, collectively, to the accompanyingselling stockholders named under the heading “Selling Stockholders” in this prospectus supplement

PROSPECTUS SUMMARY

This prospectus summary highlights certain information about us and selected information contained elsewhere in or incorporated by reference in these documents. No dealer, salesperson or other personinto this prospectus. This prospectus summary is authorized to give anynot complete and does not contain all of the information or to represent anything not containedthat you should consider before making an investment decision. For a more complete understanding of the Company, you should read and consider carefully the more detailed information included or incorporated by reference in this prospectus or the accompanying prospectus supplement. If anyone provides you with different, inconsistent or unauthorized information or representations, you must not rely on them. This prospectus and the accompanying prospectus supplement are an offer to sell only the securities offered by these documents, but only under circumstances and in jurisdictions where it is lawful to do so. The information contained in this prospectus or any prospectus supplement is current only as of the date on the front of those documents.

EXPLANATORY NOTE

This Registration Statement relates to securities being registered pursuant to Rule 415 of the Securities Act of 1933, as amended, which may be offered from time to time on a delayed or continuous basis by Delcath Systems, Inc. This Registration Statement contains a form of base prospectus relating to Delcath Systems, Inc. which will be used in connection with an offering of securities by Delcath Systems, Inc. The specific terms of the securities to be offered will be set forth in a prospectus supplement relating to such securities, other than with respect to the outstanding warrants issued under our registration statement on Form S-3, declared effective by the SEC on October 9, 2012 (No. 333-183675), which we refer to as the Prior Registration Statement, where the common shares issued upon due exercise of such warrants shall be registered hereunder.

PROSPECTUS SUMMARY

This summary highlights information contained elsewhere or incorporated by reference into this prospectus. It does not contain all the information you need to consider in making your investment decision. You should read this entire prospectus carefully, including the section entitled “Risk Factors,” any applicable prospectus supplement andor amendment, including the documents that we incorporate by reference intofactors described under the heading “Risk Factors,” beginning on page 12 of this prospectus, andas well as the prospectus supplement,information incorporated herein by reference, before making an investment decision. In this prospectus, except as otherwise indicated, “Delcath,” “Delcath Systems,” “we,” “our,”

Overview of the Company

We are an interventional oncology company focused on the treatment of primary and “us” refer to Delcath Systems, Inc.metastatic liver cancers. Our lead product candidate, the HEPZATO^™ KIT (melphalan hydrochloride for injection/hepatic delivery system), a Delaware corporation and its subsidiaries. “Delcath” is our registered United States trademark.

About Delcath

Delcath Systems, Inc.or HEPZATO^™, is a late-stage clinical development company with earlydrug/device combination product. HEPZATO is designed to administer high-dose chemotherapy to the liver while controlling systemic exposure and associated side effects. HEPZATO has not been approved for sale in the United States. In Europe, our commercial activity in Europe focused onproduct is a stand-alone medical device having the same device components as the HEPZATO KIT but without the melphalan hydrochloride. The device is approved for sale under the trade name CHEMOSAT^® Hepatic Delivery System for Melphalan, or CHEMOSAT, where it has been used at major medical centers to treat a wide range of cancers of the liver.

In the United States, HEPZATO is regulated as a combination drug and device by the United States Food and Drug Administration, or the FDA. Primary jurisdiction for regulation of HEPZATO has been assigned to the FDA’s Center for Drug Evaluation and Research. The FDA has granted the active moiety melphalan hydrochloride five orphan drug designations for the treatment of patients with ocular (uveal) melanoma, cutaneous melanoma, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and neuroendocrine tumors. The FDA has granted the active moiety doxorubicin one orphan drug designation for the treatment of patients with hepatocellular carcinoma. In Europe, CHEMOSAT is regulated as a Class IIb medical device and received its CE Mark in 2012. We are a specialty pharmaceuticalcommercializing CHEMOSAT in select markets in the United Kingdom and medical device company developing our proprietary product—Melphalan Hydrochloridethe European Union, or the EU, where we believe the prospect of securing reimbursement coverage for Injection forthe use with the Delcath Hepatic Delivery System (Melphalan/HDS). In Europe, our proprietary system to deliver and filter melphalan hydrochlorideof CHEMOSAT is marketed as a device under the trade name Delcath Hepatic CHEMOSAT^® Delivery System for Melphalan (CHEMOSAT).strongest.

Our primary focus is on the execution of our clinicalmost advanced development program is for the use of HEPZATO in the treatment of ocular melanoma liver metastases, (mOM),or mOM, a type of primary liver cancer. HEPZATO is being studied in the FOCUS Clinical Trial for Patients with Hepatic Dominant Ocular Melanoma, or the FOCUS Trial, which is a global registration clinical trial that is investigating objective response rate in mOM. The FOCUS Trial is being conducted at approximately 30 sites in the United States and Europe. The FOCUS Trial initiated treatment on the final enrolled patient on October 2, 2020. The primary endpoint of the FOCUS Trial is Objective Response Rate, or ORR, as measured by RECISTv1.1, in the Intent to Treat (ITT) population. The single arm trial was powered to demonstrate a superior ORR versus checkpoint inhibitors, one of the few mOM treatment categories with a significant amount of peer reviewed publications. The checkpoint inhibitor ORR was calculated based on a meta-analysis covering 16 different publications which included 476 patients. The pooled overall response rate was 5.5% [95% CI: 3.6, 8.3]. To achieve statistical significance at a 95% Confidence Interval, the lower bound of the ORR for HEPZATO is required to exceed the 8.3% upper bound of the meta-analysis. Secondary endpoints include Duration of Response, or DOR, Disease Control Rate, or DCR, Overall Survival, or OS, and Progression-Free Survival, or PFS. Additional exploratory outcome measures include time to objective response, hepatic progression-free survival, hepatic objective response, and quality of life, safety, and other pharmacokinetic measures. Initially, the trial was a randomized controlled trial which was amended to a single arm trial given slow enrollment due to the rarity of ocular melanoma, absence of crossover to the experimental trial arm, competing clinical trials and the commercial availability of CHEMOSAT in Europe. Included in the pre-specified analyses are comparisons against the Best Alternative Care, or BAC, arm which enrolled 32 patients prior to the amendment to a single-arm trial.

We have paused a global Phase 3 clinical trial of HEPZATO in patients with intrahepatic cholangiocarcinoma, (ICC)or the ALIGN Trial, due to difficulties in enrollment. In addition to the FOCUS Trial and the ALIGN Trial, our commercial development plan also includes a registry for CHEMOSAT cases performed in Europe and support of select investigator-initiated trials, or IITs.

We are currently reviewing the incidence, unmet need, available efficacy data and development requirements for a broad set of liver cancers in order to select a portfolio of indications which will maximize the value of the HEPZATO platform. This may result in a restart of the ALIGN Trial. We believe that the disease states we are investigating and intend to investigate are unmet medical needs that represent significant market opportunities.

Recent Developments

The Focus Trial Preliminary Analysis. On March 31, 2021, Delcath released a preliminary analysis of the FOCUS trial data based on 87% of enrolled patients using prespecified analyses. An Independent Review Committee assessed an ORR of 29.2% [95% CI: 20.1, 39.8] in the ITT population, the lower bound of which exceeded the upper bound of the predefined success criteria (8.3%) for the primary ORR endpoint. In the per protocol populations, evaluable patients in the HEPZATO arm had a statistically significant improvement over BAC in prespecified endpoints including: ORR of 32.9% [95% CI: 22.8, 44.4] versus 13.8% [CI: 3.9, 31.7] for the BAC arm (Chi-square P<0.05), hepatocellular carcinoma (HCC or primary liver)Median PFS of 9.0 months [95% CI: 6.2, 11.8] versus 3.1 months ([95% CI: 2.7, 5.7] for the BAC arm (HR=0.41 p<0.001), and DCR of 70.9% [95% CI: 59.6, 80.6] versus 37.9% [95% CI: 20.7, 57.7] for the BAC arm (p<0.002). In this preliminary analysis, DOR and OS were not yet evaluable. Since not all patients were evaluable for all time points, these preliminary analyses may change as data matures.

In the HEPZATO safety population of 94 patients, 38 patients (40.4%) experienced a treatment-emergent serious adverse event. The most commonly reported treatment-emergent serious adverse events were thrombocytopenia (14.9% of patients), neutropenia (10.6% of patients), and leukopenia (4.2% of patients), which were well-manageable. 5% of patients experienced treatment-emergent serious cardiac adverse events. In all cases the events resolved with no ongoing complications. There were no treatment-related deaths in the trial.

Impact of COVID-19.The global outbreak of SARS-CoV-2, a novel strain of coronavirus that causes coronavirus disease (“COVID-19”), has adversely impacted certain other cancers that are metastaticareas of the Company’s business. These impacts included a slowing of patient recruitment in the FOCUS Trial and a reduction in the pace at which we can monitor data at our clinical trial sites. The resulting delay in completing enrollment and additional time required to monitor data caused our announcement for the top-line data from our FOCUS Trial to shift to early 2021 and to be modified to a preliminary analysis. We intend to submit a New Drug Application (“NDA”) to the liver.FDA in the first quarter of 2022 for the treatment of mOM once the FOCUS Trial has been completed. The ability to achieve this goal is contingent on our ability to monitor data at our clinical sites and, therefore, the timeline may shift as access to the clinical sites changes in response to the rapidly evolving situation. COVID-19 has also caused us to experience an increase in volatility in EU commercial product revenue. The results of the FOCUS Trial should also support securing reimbursement coverage for the use of CHEMOSAT in Europe. Additional impacts of COVID-19 on our business may arise that we are not aware of currently. The ultimate impact of the pandemic on the Company’s results of operations, financial position, liquidity, or capital resources cannot be reasonably estimated at this time.

Medical Device Directive Transition to Medical Device Regulation. The European Commission recently reviewed the Medical Device Directive legislative framework and promulgated REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC. This new Medical Device Regulation became effective on May 25, 2017, marking the start of a 3-year transition period for manufacturers selling medical devices in Europe to comply with the new medical device regulation, or MDR, which governs all facets of medical devices. The transition task is highly complex and touches every aspect of product development, manufacturing production, distribution, and post marketing evaluation. As a result of the worldwide COVID-19 pandemic, on April 17, 2020, the European

Parliament adopted the European Commission’s proposal to postpone the implementation of the MDR (EU) 2017/745 by 12 months. This urgently drafted proposal to delay the MDR is in response to the exceptional circumstances associated with the COVID-19 pandemic and the potential impact it may have had on the MDR implementation. The new Date of Application (DoA) for the MDR was May 26, 2021.

Effectively addressing these changes will require a complete review of our device operations to determine what is necessary to comply. We do not believe the MDR regulatory changes will impact our business at this time, though implementation of the medical device legislation may adversely affect our business, financial condition and results of operations or restrict our operations.

Due to COVID-related delays experienced by the medical device industry and Notified Bodies (NB) alike, Delcath has not yet achieved MDR certification. However, our current CE Mark under the Medical Device Directive remains effective until April 2024 and allows us to fully operate, in Europe, accordingly, as Delcath and our Notified Body work closely together through the certification process.

Corporate Information

We were incorporated in the State of Delaware in August 1988. Our principal executive offices are located at 1301 Avenue of the Americas, 43rd Floor,1633 Broadway, Suite 22C, New York, New York 10019. Our telephone numberis (212) 489-2100. Our website address is http://www.delcath.com.www.delcath.com. Information contained in, or accessible through, our website does not constitute any part of, and is not a part of this prospectus.

RISK FACTORS

Investing in our securities involves a high degree of risk. You should consider carefully the risk factors set forth in the documents and reports filed by us with the Securities and Exchange Commission, which we refer to as the SEC, that are incorporated by reference into this prospectus, as well as any risks described in any applicable prospectus supplement, before deciding whether to buy our securities. Additional risks not known to us or that we believe are immaterial may also significantly impair our business operations and could result in a complete loss of your investment.

CAUTIONARY STATEMENT CONCERNING FORWARD-LOOKING STATEMENTS

This prospectus and the documents incorporated by reference into this prospectus contain certain “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995 with respect to our business, financial condition, liquidity and results of operations. Words such as “anticipates,” “expects,” “intends,” “plans,” “predicts,” “believes,” “seeks,” “estimates,” “could,” “would,” “will,” “may,” “can,” “continue,” “potential,” “should,” and the negative of these terms or other comparable terminology often identify forward-looking statements. Statements in this prospectus and the documents incorporated by reference that are not historical facts are hereby identified as “forward-looking statements” for the purpose of the safe harbor provided by Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended. These forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results to differ materially from the results contemplated by the forward-looking statements, including the risks discussed in this prospectus, in our Annual Report on Form 10-K for the fiscal year ended December 31, 2014 in Item 1A under “Risk Factors” “ as well as in Item 7A “Quantitative and Qualitative Disclosures About Market Risk” and the risks detailed from time to time in our future SEC reports. These forward-looking statements include, but are not limited to, statements about:

Many of the important factors that will determine these results are beyond our ability to control or predict. You are cautioned not to put undue reliance on any forward-looking statements, which speak only as of the date of this prospectus or, in the case of documents incorporated by reference, as of the date of such documents. Except as otherwise required by law, we do not assume any obligation to publicly update or release any revisions to these forward-looking statements to reflect events or circumstances after such applicable date or to reflect the occurrence of unanticipated events.

WHERE YOU CAN FIND ADDITIONAL INFORMATION

This prospectus is part of a registration statement we filed with the SEC. You should rely only on the information contained in this prospectus, any applicable prospectus supplement or documents incorporated by reference into, this prospectus. We have not authorized anyone else to provide you with different information. We are not making an offer of these securities in any state where the offer is not permitted. You should not assume that the information in this prospectus is accurate as of any date other than the date on the front page of this prospectus, regardless of the time of delivery of this prospectus or any sale of securities.

surrender to the Company for cancellation, warrants to purchase 5,605 shares of our Common Stock (the “Series D Warrants”) and warrants to purchase 0.1 million shares of our Common Stock (the “Pre-Funded Series D Warrants”). Under the terms of the note purchase agreement, the Company agreed to sell and issue to Rosalind 8% Senior Secured Promissory Notes (“Convertible Notes”) in whichan aggregate principal amount of $2,000,000 secured by a security interest in all assets of the debt securities will be paid or denominated;

DESCRIPTION OF CAPITAL STOCK

The following description of our common stock and preferred stock, together with the additional information incorporated by reference and in any related free writing prospectuses, summarizes the material terms and provisions of our common stock and preferred stock. The following description of our capital stock does not purport to be complete and is subject to, and qualified in its entirety by, our Amended and Restated Certificate of Incorporation, as amended, and our Amended and Restated By-Laws, which are exhibits to the registration statement of which this prospectus forms a part, and by applicable law. We refer in this section to our Amended and Restated Certificate of Incorporation, as amended, as our certificate of incorporation, and we refer to our Amended and Restated By-Laws as our by-laws. The terms of our common stock and preferred stock may also be affected by Delaware law.

Authorized Capital Stock

The following is a description of the material terms of our capital stock included in our Amended and Restated Certificate of Incorporation, as amended (our “Certificate of Incorporation”), and our Amended and Restated By-Laws (our “By-Laws”). This description of our capital stock does not purport to be complete and is subject to, and qualified in its entirety by, our Certificate of Incorporation and By-Laws, which are exhibits to the registration statement of which this prospectus forms a part, and by applicable law. The terms of our common stock and preferred stock may also be affected by Delaware law.

Our authorized capital stock consists of:

Our common stock is the only class or series of our securities which has been registered under Section 12 of the Securities Exchange Act of 1934, as amended, and is listed on The Nasdaq Capital Market under the symbol “DCTH”. Of the 10,000,000 authorized shares of preferred stock, an aggregate of 52,960 shares are designated as Series E Preferred Stock or Series E-1 Preferred Stock. As of October 5, 2021, there were outstanding 7,356,289 shares of our common stock $0.01 par value per share, and 10,000,000an aggregate of 11,707.21 shares of undesignated preferred stock, $0.01 par value per share. Series E Preferred Stock and Series E-1 Preferred Stock.

As of October 1, 2015, we had 21,763,8645, 2021, there were 2,475,000 shares of the Company’s common stock outstanding and noreserved under the Delcath Systems, Inc. 2020 Omnibus Equity Incentive Plan, of which 1,255,250 shares of preferred stock outstanding.remained available to be issued. As of October 1, 2015,5, 2021, we had 18,059,000(a) 3,894,498 shares of common stock issuable upon the exercise of outstanding warrants, or optionsincluding (i) 1,758,843 Series E and Series E-1 Warrants, (ii) 1,851,900 Series F Warrants, (iii) 156,000 Series F Pre-funded Warrants and (iv) 127,755 shares of common stock that may be issued upon the exercise of a warrant to purchase warrantsAvenue Venture Opportunities Fund, LP at a weighted average exercise price of $1.00$9.27 per share 766,135and (b) 1,718,249 shares of common stock issuable upon the exercise of stockoutstanding options atwith a weighted average exercise price of $7.57$11.69 per share, and 576,086 shares of unvested restricted common stock.share.

Common Stock

Voting rights.

Holders Our shares of our common stock are entitled to voting rights for the election of directors and for all other matters requiring stockholder action. Each holder of common stock is entitled to one vote perfor each share, on mattersexcept as otherwise required by law, and subject to be voted on by stockholders and alsothe rights of the holders of preferred stock. The common stock does not have cumulative voting rights.

Dividend rights. Holders of our common stock are entitled to receive such dividends, if any, as may be declared from time to time by our board of directors in its discretion out of funds legally available therefor. Holders of our common stock have exclusive voting rights for the election of our directors and all other matters requiring stockholder action, except with respect to amendments to our certificate of incorporation that alter or change the powers, preferences, rights or other terms of any outstanding preferred stock if the holders of such affected series of preferred stock are entitled to vote on such an amendment or filling vacancies on the board of directors.

Dividends

Holders of common stock are entitled to share ratably in any dividends declared by our board of directors, subject to any preferential dividend rights of any outstanding preferred stock. Dividends consisting of shares of common stock may be paid to holders of shares of common stock. We do not intend to pay cash dividends in the foreseeable future.

Liquidation and Dissolutionrights.

Upon our liquidation or dissolution, the holders of our common stock will be entitled to receive, pro rata, all assets remaining available for distribution to stockholders after payment of all liabilities and provision for the liquidation of any shares of preferred stock at the time outstanding.

Other Rights and Restrictions

. Our common stock has no preemptive or other subscription rights, and there are no conversion rights or redemption or sinking fund provisions with respect to such stock. Our common stock is not subject to redemption

by us. Our certificateCertificate of incorporationIncorporation and bylawsBylaws do not restrict the ability of a holder of common stock to transfer the stockholder’s shares of common stock. If we issue shares of common stock under this prospectus, the shares will be fully paid and non-assessable and will not have, or be subject to, any preemptive or similar rights.

Listing

Market Information. Our common stock is listedtraded on The NASDAQthe Nasdaq Capital Market under the symbol “DCTH.”“DCTH”.

Transfer Agent and Registrar

. The transfer agent and registrar for our common stock is American Stock Transfer & Trust Company.Company, LLC

Preferred Stock

Our board of directors has the authority to issue up to 10,000,000 shares of preferred stock in one or more series and to determine the rights and preferences of the shares of any such series without stockholder approval, none of which are outstanding.11,707.21 shares of Series E Preferred Stock and Series E-1 Preferred Stock, or, collectively, the Preferred Stock, is outstanding as of October 5, 2021. Our board of directors may issue preferred stock in one or more series and has the authority to fix the designation and powers, rights and preferences and the qualifications, limitations, or restrictions with respect to each class or series of such class without further vote or action by the stockholders. The ability of our board of directors to issue preferred stock without stockholder approval could have the effect of delaying, deferring or preventing a change of control of us or the removal of existing management.

Certain In connection with a private placement in July 2019, the Company filed a certificate of designation of Preferences, Rights and Limitations of Series E Preferred Stock with the Secretary of State of the State of Delaware, or the Delaware SOS, for the purpose of amending its Certificate of Incorporation to classify and designate 40,000 authorized but unissued shares of the Company’s preferred stock as shares of Series E Preferred Stock. The preferences, conversion and other rights, voting powers, restrictions, limitations as to dividends and other distributions, qualifications and terms and conditions of redemption of the Series E Preferred Stock are set forth in the Certificate of Designation and are described below. The certificate of designation became effective on July 11, 2019 upon acceptance for filing by the Delaware SOS.

In connection with a private placement in August 2019, the Company filed a certificate of designation of Preferences, Rights and Limitations of Series E-1 Preferred Stock with Delaware SOS, for the purpose of amending its Certificate of Incorporation to classify and designate 12,960 authorized but unissued shares of the Company’s preferred stock as shares of Series E-1 Preferred Stock. The preferences, conversion and other rights, voting powers, restrictions, limitations as to dividends and other distributions, qualifications and terms and conditions of redemption of the Series E-1 Preferred Stock are set forth in the certificate of designation and are described below. The certificate of designation became effective on August 15, 2019 upon acceptance for filing by the Delaware SOS.

Conversion rights. Each share of the Series E Preferred Stock and Series E-1 Preferred Stock has a par value of $0.01 per share and a stated value equal to $1,000, or the Stated Value, and is convertible at any time at the option of the holder into the number of shares of common stock determined by dividing the stated value by the conversion price of $10.00, subject to certain limitations and adjustments, or the Conversion Price.

Voting rights. The Preferred Stock votes an as converted basis on all matters submitted to the holders of common stock for approval, subject to certain limitations and exceptions. The affirmative vote of the holders of a majority of the then outstanding shares of Preferred Stock is required to increase the number of authorized shares of Preferred Stock or to alter or change adversely the powers, preferences or rights given to the Preferred Stock, or to amend the Company’s organizational documents in any manner that adversely affects the rights of the holders of the Preferred Stock.

Dividend rights. Except for certain adjustments, the holders of Preferred Stock are entitled to receive dividends on shares of Preferred Stock equal (on an as if converted basis) to and in the same form as dividends paid on shares of the common stock. Any such dividends that are not paid to the holders of Preferred Stock will increase the Stated Value. No other dividends will be paid on shares of Preferred Stock.

Liquidation rights. Upon any liquidation of the Company, the holders of Preferred Stock will be entitled to receive out of the assets of the Company an amount equal to the Stated Value plus any accrued and unpaid dividends thereon for each share of Preferred Stock before any distribution or payment will be made to the holders of the common stock.

Anti-Takeover ProvisionsEffects of Delaware Law and Our Certificate of Incorporation and Bylaws

Certain provisions of our Certificate of Incorporation and Bylaws could have the effect of making it more difficult for our stockholders to replace management at a time when a substantial number of stockholders might favor a change in management. These provisions include:

Furthermore, our board of directors has the authority to issue up to 9,929,890 shares of preferred stock in one or more series and to determine the rights and preferences of the shares of any such series without stockholder approval. Any series of preferred stock is likely to be senior to the common stock with respect to dividends, liquidation rights and, possibly, voting rights. The board’s ability to issue preferred stock may have the effect of discouraging unsolicited acquisition proposals, thus adversely affecting the market price of our common stock.

We are not subject to Section 203 of the Delaware General Corporation Law, which prohibits Delaware corporations from engaging in a wide range of specified transactions with any interested stockholder, defined to include, among others, any person other than such corporation and any of its majority owned subsidiaries who own 15% or more of any class or series of stock entitled to vote generally in the election of directors, unless, among other exceptions, the transaction is approved by (i) our board of directors prior to the date the interested stockholder obtained such status or (ii) the holders of two thirdstwo-thirds of the outstanding shares of each class or series of stock entitled to vote generally in the election of directors, not including those shares owned by the interested stockholder.

Staggered Board of DirectorsDirectors.

Our certificateCertificate of incorporationIncorporation and by-lawsBylaws provide that our board of directors be classified into three classes of directors of approximately equal size. As a result, in most circumstances, a person can gain control of our board only by successfully engaging in a proxy contest at two or more annual meetings.

Authorized Butbut Unissued SharesShares.

Our authorized but unissued shares of common stock and preferred stock are available for future issuances without stockholder approval and could be utilized for a variety of corporate purposes, including future offerings to raise additional capital, corporate acquisitions, employee benefit plans and stockholder rights plans. The existence of authorized but unissued and unreserved common stock and preferred stock could render more difficult or discourage an attempt to obtain control of us by means of a proxy contest, tender offer, merger or otherwise.

DESCRIPTION OF STOCK PURCHASE CONTRACTSTHE OFFERING

The following description, together

RISK FACTORS

An investment in our Common Stock involves a high degree of risk. Prior to making a decision about investing in our Common Stock, you should consider carefully the specific risk factors discussed in the sections entitled “Risk Factors” contained in our most recent Annual Report on Form 10-K for the year ended December 31, 2020, as filed with the additional informationSEC on March 31, 2021, which are incorporated in this prospectus by reference in their entirety. Additional risk factors that we includeyou should carefully consider may be included in our subsequent filings with the SEC, including a prospectus supplement or amendment hereto relating to an offering of our Common Stock by us or the Selling Stockholders. The risks and uncertainties described in this prospectus, any applicable prospectus supplement or amendment, and inthe documents incorporated by reference herein are not the only risks and uncertainties we face. Additional risks and uncertainties not presently known to us, or that we currently view as immaterial, may also impair our business. If any related free writing prospectuses, summarizes the material terms and provisions of the stock purchase contracts that we may offer under this prospectus. While the terms we have summarized below will apply generally to any stock purchase contracts that we may offer underrisks or uncertainties described in this prospectus, we will describe the particular terms of any series of stock purchase contracts in more detail in the applicable prospectus supplement. The termssupplement or amendment, or the documents incorporated by reference herein actually occur, our business, financial condition, results of any stock purchase contracts offered under aoperations and cash flow could be materially and adversely affected. In that case, the trading price of our Common Stock could decline, perhaps significantly, and you might lose part or all of your investment.

CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

This prospectus, supplement may differ fromand the terms described below.

Wedocuments incorporated by reference herein, contain, or will filecontain, “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as exhibits“intends,” “believes,” “anticipates,” “indicates,” “plans,” “expects,” “suggests,” “may,” “would,” “should,” “potential,” “designed to,” “will,” “ongoing,” “estimate,” “forecast,” “predict,” “could,” and similar references, although not all forward-looking statements contain these words. Forward-looking statements are neither historical facts nor assurances of future performance. These statements are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the registration statement of which this prospectus is a part, or will incorporate by reference from reports that we file with the SEC, the form of stock purchase contract that describes the terms of the particular stock purchase contract we are offering before the issuance of the related stock purchase contract. The following summaries of material provisions of the stock purchase contractsfuture, they are subject to inherent uncertainties, risks and qualifiedchanges in their entirety by referencecircumstances that are difficult to all predict and many of which are outside of our control. Risks that could cause actual results to vary from expected results expressed in our forward-looking statements include, but are not limited to:

Forward-looking statements speak only as of the date the statements are made. Except as required under the federal securities laws and rules and regulations of the SEC, we undertake no obligation to update or revise forward-looking statements to reflect actual results, changes in assumptions or changes in other factors affecting forward-looking information. We caution you not to unduly rely on the forward-looking statements when evaluating the information presented herein.

USE OF PROCEEDS

We will not receive any of the proceeds from the shares of Common Stock sold by the Selling Stockholders hereunder. However, assuming (i) the conversion of all of the Series E Preferred Stock following an election to convert the principal amount and all accrued interest under the 8% senior secured promissory notes into such shares, (ii) the conversion of the entire convertible portion of the Loan and (iii) the exercise of the Warrant, we will receive, upon issuance of the Common Stock to the Selling Stockholders $1,278 upon exercise of the Warrant (which will be used for working capital purposes), the outstanding principal amount of the Loan will be reduced by $3 million and the complete stock purchase contracts that contain8% senior secured promissory notes will be no longer be outstanding. We have agreed to pay all costs, expenses and fees relating to the termsregistration of the stock purchase contracts.shares of Common Stock covered by this prospectus.

WeSELLING STOCKHOLDERS

The Selling Stockholders, or each of their donees, pledgees, assignees, transferees or other successors-in-interest, are offering for resale, from time to time, up to an aggregate of 638,199 shares of Common Stock. The shares of Common Stock covered by this prospectus represent all the shares of Common Stock that have been or may issue stock purchase contracts, including contracts obligating holders to purchase from us and us to sellbe issued to the holders, a specifiedSelling Stockholders in connection with the transactions described under the heading “The Offering” on page 11 of this prospectus. The following table sets forth certain information with respect to beneficial ownership of our Common Stock as of October 5, 2021 by the Selling Stockholders, as determined in accordance with Rule 13d-3 of the Exchange Act of 1934, as amended (the “Exchange Act”), prior to this offering and after this offering. This information has been obtained from the Selling Stockholders or in Schedules 13G or 13D and other public documents filed with the SEC.

The number of shares of common stockCommon Stock beneficially owned after this offering assumes the sale of all of the Common Stock offered by the Selling Stockholders pursuant to this prospectus. However, because the Selling Stockholders may sell none, some or preferred stock at a future dateall of the shares of Common Stock covered by this prospectus from time to time, or dates. Alternatively,in another permitted manner, we cannot assure you as to the stock purchase contracts may obligate us to purchase from holders, and obligate holders to sell to us, a specified or varyingactual number of shares of common stockCommon Stock that will be sold by the Selling Stockholders or preferred stock. The consideration per sharethat will be held by the Selling Stockholders after completion of common stock or preferred stock may be fixed atany sales. We do not know how long the timeSelling Stockholder will hold the stock purchase contracts are issued or may be determined by a specific reference to a formula set forth in the stock purchase contracts. The stock purchase contracts may provide for settlement by delivery by us or on our behalf of shares of Common Stock covered by this prospectus before selling them. Information concerning the underlying security, or theySelling Stockholders may provide for settlement by reference or linkagechange from time to the value, performance or trading price of the underlying security. The stock purchase contracts may require us to make periodic payments to the holders of the certain of our securities or vice versa,time and such payments maychanged information will be unsecured or prefunded on some basis and may be paid on a current or on a deferred basis. The stock purchase contracts may require holders to secure their obligations thereunderpresented in a specified manner and may provide for the prepayment of all or part of the consideration payable by holders in connection with the purchase of the underlying security or other property pursuant to the stock purchase contracts.

The securities related to the stock purchase contracts may be pledged to a collateral agent for our benefit pursuant to a pledge agreement to secure the obligations of holders of stock purchase contracts to purchase the underlying security or property under the related stock purchase contracts. The rights of holders of stock purchase contracts to the related pledged securities will be subject to our security interest therein created by the pledge agreement. No holder of stock purchase contracts will be permitted to withdraw the pledged securities related to such stock purchase contracts from the pledge arrangement.

DESCRIPTION OF WARRANTS

The following description, together with the additional information we may include in any applicable prospectus supplement summarizes the material terms and provisions of the warrants that we may offer under this prospectus and the related warrant agreements and warrant certificates. While the terms summarized below will apply generally to any warrants that we may offer, we will describe the particular terms of any series of warrants in more detail in the applicable prospectus supplement. The terms of any warrants offered under a prospectus supplement may differ from the terms described below.

We will file as exhibits to the registration statement of which this prospectus is a part, or will incorporate by reference from reports that we file with the SEC, the form of warrant agreement, including a form of warrant certificate, that describes the terms of the particular warrants we are offering before the issuance of the related warrants. The following summaries of material provisions of the warrants and the warrant agreements are subject to, and qualified in their entirety by reference to, all the provisions of the warrant agreement and warrant certificate applicable to the warrants that we may offer under this prospectus. We urge you to read the applicable prospectus supplements related to the warrants that we may offer under this prospectus, as well as any related free writing prospectuses, and the complete warrant agreements and warrant certificates that contain the terms of the warrants.

General

We may issue warrants for the purchase of common stock or preferred stock in one or more series. We may issue warrants independently or together with common stock and preferred stock, and the warrants may be attached to or separate from these securities.

We may evidence each series of warrants by warrant certificates that we will issue under a separate agreement. We may enter into a warrant agreement with a warrant agent. We will indicate the name and address and other information regarding the warrant agent in the applicable prospectus supplement relating to a particular warrants.

If we decide to issue warrants pursuant to this prospectus we will specify inif and when necessary and required. However, the Selling Stockholders may sell or transfer all or a portion of their shares of Common Stock covered by this prospectus supplementpursuant to any available exemption from the termsregistration requirements of the warrants, including, if applicable, the following:Securities Act.

SELLING STOCKHOLDER TABLE

Relationship with Selling Stockholders

On April 8, 2020, we entered into a Board Appointment Agreement, dated as of April 8, 2020, with Rosalind Opportunities Fund I L.P. and aggregate numberRosalind Maser Fund L.P. (“Rosalind”), pursuant to which Steven Salamon and Gil Aharon, who are principals of warrants offered;

PLAN OF DISTRIBUTION

We may sellare registering the securities offeredshares of Common Stock issued, or issuable upon the conversion of Series E Preferred Stock, to the Selling Stockholders to permit the resale of those shares of Common Stock by this prospectusthe holders of the shares of Common Stock from time to time after the date of this prospectus. We will not receive any of the proceeds from the sale by the Selling Stockholders of the shares of Common Stock. We will bear all fees and expenses incident to our obligation to register the shares of Common Stock.

The Selling Stockholders may sell all or a portion of the share of Common Stock beneficially owned by them and offered hereby from time to time directly or through one or more underwriters, broker-dealers or agents. If the Shares are sold through underwriters or broker-dealers, the Selling Stockholders will be responsible for underwriting discounts or commissions or agent’s commissions. The shares of Common Stock may be sold on any national securities exchange or quotation service on which the securities may be listed or quoted at the time of sale, in the over-the-counter market or in transactions otherwise than on these exchanges or systems or in the over-the-counter market and in one or more transactions including without limitation:

WeIn connection with sales of the shares of Common Stock, the Selling Stockholders may also enter into hedging transactions. For example, we may:

shares in the course of hedging in positions they assume. The Selling Stockholders may also sell shares short and if such short sale shall take place after the date that the registration statement of which this prospectus in which case such broker-dealer or affiliateis a part is declared effective by the SEC, the Selling Stockholders may usedeliver the shares of common stock received from uscovered by this prospectus to close out its short positions;

The Selling Stockholders and their affiliates,any other person participating in such distribution will be subject to applicable provisions of the Exchange Act, and the rules and regulations thereunder, including, without limitation, Regulation M of the Exchange Act, which may engage in transactions with, or perform services for, us inlimit the ordinary coursetiming of business. This includes commercial bankingpurchases and investment banking transactions.

Market-Making, Stabilization and Other Transactions

There is currently no market forsales of any of the offered securities,shares of Common Stock by the Selling Stockholders and any other thanparticipating person. Regulation M may also restrict the common stock which is listed on the NASDAQ Capital Market. If the offered securities are traded after their initial issuance, they may trade at

a discount from their initial offering price, depending upon prevailing interest rates, the market for similar securities and other factors. While it is possible that an underwriter could inform us that it intends to make a marketability of any person engaged in the offered securities, such underwriter would not be obligated to do so, and any such market-making could be discontinued at any time without notice. Therefore, no assurance can be given as to whether an active trading market will develop for the offered securities. We have no current plans for listingdistribution of the debt securities, preferred stock or warrants on any securities exchange or on the National Associationshares of Securities Dealers, Inc. automated quotation system; any such listingCommon Stock to engage in market-making activities with respect to any particular debt securities, preferred stock or warrants will be described in the applicable prospectus supplement or pricing supplement, as the case may be.

In connection with any offering of common stock, the underwriters may purchase and sell shares of common stock in the open market. These transactions may include short sales, syndicate covering transactions and stabilizing transactions. Short sales involve syndicate sales of common stock in excessshares. All of the number of shares to be purchased byforegoing may affect the underwriters in the offering, which creates a syndicate short position. “Covered” short sales are sales of shares made in an amount up to the number of shares represented by the underwriters’ over-allotment option. In determining the source of shares to close out the covered syndicate short position, the underwriters will consider, among other things, the price of shares available for purchase in the open market as compared to the price at which they may purchase shares through the over-allotment option. Transactions to close out the covered syndicate short involve either purchases of the common stock in the open market after the distribution has been completed or the exercise of the over-allotment option. The underwriters may also make “naked” short sales of shares in excess of the over-allotment option. The underwriters must close out any naked short position by purchasing shares of common stock in the open market. A naked short position is more likely to be created if the underwriters are concerned that there may be downward pressure on the pricemarketability of the shares inand the open market after pricing that could adversely affect investors who purchase in the offering. Stabilizing transactions consistability of bids forany person or purchases of shares in the open market while the offering is in progress for the purpose of pegging, fixing or maintaining the price of the securities.

In connection with any offering, the underwriters may alsoentity to engage in penalty bids. Penalty bids permitmarket-making activities with respect to the underwriters to reclaim a selling concession from a syndicate member when the securities originally sold by the syndicate member are purchased in a syndicate covering transaction to cover syndicate short positions. Stabilizing transactions, syndicate covering transactions and penalty bids may cause the price of the securities to be higher than it would be in the absence of the transactions. The underwriters may, if they commence these transactions, discontinue them at any time.shares.

LEGAL MATTERS

Unless otherwise indicated in the applicable prospectus supplement, Morgan, Lewis & Bockius LLP, New York, New York will provide opinions regarding the authorization andThe validity of the securities. Morgan, Lewis & Bockius LLP may also provide opinions regarding certain other matters. Any underwriters will alsoshares of Common Stock to be advised about legal mattersoffered for resale by their own counsel, whichthe Selling Stockholder under this prospectus will be named in the prospectus supplement.passed upon for us by McCarter & English, LLP, Newark, New Jersey.

EXPERTS

The consolidated financial statements as of Delcath Systems, Inc. at December 31, 20142020 and 20132019 and for each of the threetwo years in the period ended December 31, 2014 included2020 incorporated by reference in Delcath Systems, Inc.’s Annual Report (Form 10-K) for the year ended December 31, 2014,this prospectus have been audited by Ernst & Youngso incorporated in reliance on the report of Marcum, LLP, predecessoran independent registered public accounting firm, as set forth in their respective report thereon, included therein, and incorporated herein by reference, in reliance upon such report given on the authority of suchsaid firm as experts in accountingauditing and auditing.

WHERE YOU CAN FIND MORE INFORMATION AND INCORPORATION OF CERTAIN INFORMATION BY REFERENCE

The SEC allows us to incorporate by reference into this prospectus the information contained in other documents we file with the SEC, which means that we can disclose important information to you by referring you to those documents. Any statement contained in any document incorporated or deemed to be incorporated by reference herein shall be deemed to be modified or superseded, for purposes of this prospectus, to the extent that a statement contained in or omitted from this prospectus, or in any other subsequently filed document that also is or is deemed to be incorporated by reference herein, modifies or supersedes such statement. Any such statement so modified or superseded shall not be deemed, except as so modified or superseded, to constitute a part of this prospectus. We incorporate by reference the documents listed below which have been filed by us:

All documents we file with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act, except as to any portion of any report or documents that is not deemed filed under such provisions, (1) on or after the date of filing of the registration statement containing this prospectus and prior to the effectiveness of the registration statement and (2) on or after the date of this prospectus until the earlier of the date on which all of the securities registered hereunder have been sold or the registration statement of which this prospectus is a part has been withdrawn, shall be deemed incorporated by reference in this prospectus and to be a part of this prospectus from

the date of filing of those documents and will be automatically updated and, to the extent described above, supersede information contained or incorporated by reference in this prospectus and previously filed documents that are incorporated by reference in this prospectus.

Nothing in this prospectus shall be deemed to incorporate information furnished but not filed with the SEC pursuant to Item 2.02, 7.01 or 9.01 of Form 8-K. Upon written or oral request, we will provide without charge to each person, including any beneficial owner, to whom a copy of the prospectus is delivered a copy of any or all of the reports or documents incorporated by reference herein (other than exhibits to such documents, unless such exhibits are specifically incorporated by reference herein). You may request a copy of these filings, at no cost, by writing or telephoning us at the following address: Delcath Systems, Inc., 1633 Broadway, Suite 22C, New York, New York 10019.

We maintain a website at www.delcath.com. You may access our definitive proxy statements on Schedule 14A, annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and periodic amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act with the SEC free of charge at our website as soon as reasonably practicable after such material is electronically filed with, or furnished to, the SEC. The information contained in, or that can be accessed through, our website is not incorporated by reference in, and is not part of, this prospectus. You should not consider the contents of our website in making an investment decision with respect to our common stock.

We have not authorized any one to provide you with any information that differs from that contained in this prospectus. Accordingly, you should not rely on any information that is not contained in this prospectus. You should not assume that the information in this prospectus is accurate as of any date other than the date of the front cover of this prospectus.

The SEC maintains an Internet site that contains all reports and other information that we file electronically with the SEC. The address of that website is www.sec.gov.

* * *

Up to 638,199 Shares of

Common Stock Offered by the Selling Stockholders

PROSPECTUS

                , 2021

We have not authorized any dealer, salesperson or other person to give any information or represent anything not contained in this prospectus. You must not rely on any unauthorized information. If anyone provides you with different or inconsistent information, you should not rely on it. This prospectus does not offer to sell any securities in any jurisdiction where it is unlawful. Neither the delivery of this prospectus, nor any sale made hereunder, shall create any implication that the information in this prospectus is correct after the date hereof.

PART II

INFORMATION NOT REQUIRED IN THE PROSPECTUS

The following table sets forth various expenses relating tobeing borne by the registrationCompany in connection with the sale and distribution of the securities will be borne bybeing registered. All of the registrant. Such expenses (exceptamounts shown are estimates except for the SECSecurities and Exchange Commission Registration Fee) are estimated to be as follows:Fee.

The registrant’sCompany is incorporated under the laws of the State of Delaware. Section 102(b)(7) of Delaware’s General Corporation Law (the “DGCL”) allows a corporation to provide in its certificate of incorporation that a director of the corporation will not be personally liable to the corporation or its stockholders for monetary damages for breach of fiduciary duty as a director, except where the director breached the duty of loyalty, failed to act in good faith, engaged in intentional misconduct or knowingly violated a law, authorized the payment of a dividend or approved a stock repurchase in violation of Delaware corporate law or obtained an improper personal benefit. Our amended and restated certificate of incorporation as amended, contains provisions permitted under Delaware law relating to the liabilityprovides for this limitation of directors. These provisions eliminate a director’s personal liability for monetary damages resulting from a breach of fiduciary duty, except in circumstances involving wrongful acts, such as:liability.

These provisions do not limitofficer, employee or eliminate the registrant’s rightsagent of another corporation or any stockholder’s rights to seek non-monetary relief, such as an injunction or rescission, in the event of a breach of a director’s fiduciary duty. These provisions will not alter a director’s liability under federal securities laws.

enterprise. The registrant has entered into indemnification agreements with each of its directors and executive officers that require it to indemnify such persons against any and allindemnity may include expenses (including attorneys’ fees), witness fees, judgments, fines settlements and other amounts paid in settlement actually and reasonably incurred (including expenses of a derivative action)by such person in connection with anysuch action, suit or proceeding, provided such person acted in good faith and in a manner he reasonably believed to be in or alternative dispute resolution mechanism, inquiry hearingnot opposed to the corporation’s best interests and, with respect to any criminal action or investigation, whetherproceeding, had no reasonable cause to believe that his or her conduct was illegal. A Delaware corporation may indemnify any persons who are, were or are a party to any threatened, pending or completed to which any such person may be made a partyaction or suit by or in the right of the corporation by reason of the fact that such person is or was a director, officer, employee or agent of another corporation or enterprise. The indemnity may include expenses (including attorneys’ fees) actually and reasonably incurred by such person in connection with the defense or settlement of such action or suit, provided such person acted in good faith and in a manner he reasonably believed to be in or not opposed to the corporation’s best interests, provided that no indemnification is permitted without judicial approval if the officer, director, employee or agent is adjudged to be liable to the corporation. Where an officer or andirector is successful on the merits or otherwise in the defense of any action referred to above, the corporation must indemnify him against the expenses which such officer or director has actually and reasonably incurred.

Section 145 further authorizes a corporation to purchase and maintain insurance on behalf of any person who is or was a director, officer, employee or agent of the registrantcorporation or is or was serving at the request of the Companycorporation as a director, officer, employee or employeeagent of another corporation limitedor enterprise, against any liability company, partnershipasserted against him and incurred by him in any such capacity, or other enterprise, providedarising out of his or her status as such, whether or not the corporation would otherwise have the power to indemnify him under Section 145.

Article SEVENTH of the Company’s amended and restated certificate of incorporation provides that such person’s conduct did not constituteno person serving as a director of the Company shall be personally liable to the Company or its stockholders for

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breach of his or her fiduciary duty as a director, except where the director breached his duty of loyalty, failed to the registrant or its stockholders, and was not an act or omission not in good faith, or which involvedengaged in intentional misconduct or a knowing violation of laws. law, authorized the payment of a dividend or approved a stock repurchase in violation of the DGCL or obtained an improper personal benefit.

Article EIGHTH of the Company’s amended and restated certificate of incorporation requires the Company to indemnify any person who may be indemnified by a Delaware corporation pursuant to Section 145 of the DGCL in each situation where the Company is permitted to indemnify such persons.

We have entered into indemnification agreements with our executive officers and directors pursuant to which we have agreed to indemnify such persons against all expenses and liabilities incurred or paid by such person in connection with any proceeding arising from the fact that such person is or was an officer or director of our company, and to advance expenses as incurred by or on behalf of such person in connection therewith.

The indemnification agreements alsorights set forth certain proceduresabove shall not be exclusive of any other right which an indemnified person may have or hereafter acquire under any statute, provision of our certificate of incorporation, our bylaws, agreement, vote of stockholders or disinterested directors or otherwise.

In addition, we maintain standard policies of insurance that

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TheA list of exhibits filed with this registration statement on Form S-3 is set forth on the Exhibit Index beginning on page II-5and is hereby incorporated herein by reference.

(a) The undersigned Registrant hereby undertakes:

(a)

(1) To file, during any period in which offers or sales are being made, a post-effective amendment to this registration statement:Registration Statement:

(i) toTo include any prospectus required by Sectionsection 10(a)(3) of the Securities Act;Act of 1933;

(ii) toTo reflect in the prospectus any facts or events arising after the effective date of the registration statementRegistration Statement (or the most recent post-effective amendment thereof) which, individually or in the aggregate, represent a fundamental change in the information set forth in the registration statement.Registration Statement. Notwithstanding the foregoing, any increase or decrease in volume of securities offered (if the total dollar value of securities offered would not exceed that which was registered) and any deviation from the low or high end of the estimated maximum offering range may be reflected in the form of prospectus filed with the Securities and Exchange Commission (the “Commission”) pursuant to Rule 424(b) if, in the aggregate, the changes in volume and price represent no more than 20 percent20% change in the maximum aggregate offering price set forth in the “Calculation of Registration Fee” table in the effective registration statement; andRegistration Statement.

(iii) toTo include any material information with respect to the plan of distribution not previously disclosed in the registration statementRegistration Statement or any material change to such information in the registration statement;Registration Statement;

provided, however that:

Paragraphs (i), (ii)that paragraphs a(i), a(ii) and (iii)a(iii) do not apply if the information required to be included in a post-effective amendment by those paragraphs is contained in reports filed with or furnished to the Commission by the Registrantregistrant pursuant to Section 13 or Section 15(d) of the Securities and Exchange Act of 1934, as amended (the “Exchange Act”), that are incorporated by reference in the registration statement, or is contained in a form of prospectus filed pursuant to Rule 424(b) that is part of the registration statement.

(2) That, for the purpose of determining any liability under the Securities Act of 1933, each such post-effective amendment shall be deemed to be a new registration statement relating to the securities offered

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therein, and the offering of such securities at that time shall be deemed to be the initialbona fideoffering thereof.thereof;

(3) To remove from registration by means of a post-effective amendment any of the securities being registered which remain unsold at the termination of the offering.

(4) That, for the purpose of determining liability under the Securities Act of 1933 to any purchaser:

(i) Each prospectus filed by a Registrantthe registrant pursuant to Rule 424(b)(3) shall be deemed to be part of the registration statement as of the date the filed prospectus was deemed part of and included in the registration statement; and

(ii) Each prospectus required to be filed pursuant to Rule 424(b)(2), (b)(5), or (b)(7) as part of a registration statement in reliance on Rule 430B relating to an offering made pursuant to Rule 415(a)(1)(l)(i), (vii), or (x) for the purpose of providing the information required by Section 10(a) of the Securities Act of 1933 shall be deemed to be part of and included in the registration statement as of the earlier of the date such form of prospectus is first used after effectiveness or the date of the first contract of sale of securities in the offering described in the prospectus. As provided in Rule 430B, for liability purposes of the issuer and any person that is at that date an underwriter, such date shall be deemed to be a new effective date of the registration statement relating to the securities in the registration statement to which that prospectus relates, and the offering of such securities at that time shall be deemed to be the initialbona fideoffering thereof.Provided,thereof; provided, however,, that no statement made in a registration

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statement or prospectus that is part of the registration statement or made in a document incorporated or deemed incorporated by reference into the registration statement or prospectus that is part of the registration statement will, as to a purchaser with a time of contract of sale prior to such effective date, supersede or modify any statement that was made in the registration statement or prospectus that was part of the registration statement or made in any such document immediately prior to such effective date.date;

(5) That, for the purpose of determining liability of the Registrant under the Securities Act to any purchaser in the initial distribution of the securities, the(b) The undersigned Registrantregistrant hereby undertakes that, in a primary offering of securities of the undersigned Registrant pursuant to this registration statement, regardless of the underwriting method used to sell the securities to the purchaser, if the securities are offered or sold to such purchaser by means of any of the following communications, the undersigned Registrant will be a seller to the purchaser and will be considered to offer or sell such securities to such purchaser:

(i) Any preliminary prospectus or prospectus of the undersigned Registrant relating to the offering required to be filed pursuant to Rule 424;

(ii) Any free writing prospectus relating to the offering prepared by or on behalf of the undersigned Registrant or used or referred to by the undersigned Registrant;

(iii) The portion of any other free writing prospectus relating to the offering containing material information about the undersigned Registrant or its securities provided by or on behalf of the undersigned Registrant; and

(iv) Any other communication that is an offer in the offering made by the undersigned Registrant to the purchaser.

(6) That, for purposes of determining any liability under the Securities Act, each filing of the Registrant’sregistrant’s annual report pursuant to Section 13(a) or Section 15(d) of the Exchange Act (and, where applicable, each filing of an employee benefit plan’s annual report pursuant to Section 15(d) of the Exchange Act) that is incorporated by reference in the registration statement shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initialbona fideoffering thereof.

(7) To file an application for the purpose of determining the eligibility of the trustee to act under subsection (a) of Section 310 of the Trust Indenture Act in accordance with the rules and regulations prescribed by the SEC under Section 305(b)(2) of the Trust Indenture Act.

(b)(c) Insofar as indemnification for liabilities arising under the Securities Act may be permitted to directors, officers and controlling persons of the Registrantregistrant pursuant to the foregoing provisions, or otherwise, the Registrantregistrant has been advised that in the opinion of the Commission such indemnification is against public policy as expressed in the Securities Act and is, therefore, unenforceable. In the event that a claim for indemnification against such liabilities (other than the payment by the Registrantregistrant of expenses incurred or paid by a director, officer or controlling person of the Registrantregistrant in the successful defense of any action, suit or proceeding) is asserted by such director, officer or controlling person in connection with the securities being registered, the Registrantregistrant will, unless in the opinion of its counsel the matter has been settled by controlling precedent, submit to a court of appropriate jurisdiction the question whether such indemnification by it is against public policy as expressed in the Securities Act and will be governed by the final adjudication of such issue.

(d) The undersigned registrant hereby undertakes that: (1) for purposes of determining any liability under the Securities Act, the information omitted from the form of prospectus filed as part of this registration statement in reliance upon Rule 430A and contained in a form of prospectus filed by the registrant pursuant to Rule 424(b) (1) or (4) or 497(h) under the Securities Act shall be deemed to be part of this registration statement as of the time it was declared effective; and (2) for the purpose of determining any liability under the Securities Act, each post-effective amendment that contains a form of prospectus shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.

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Exhibit Index

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SIGNATURES

Pursuant to the requirements of the Securities Act of 1933, the registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-3 and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in New York, NY,New York, on October 7, 2015.6, 2021.

POWER OF ATTORNEY

EachKNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Jennifer K. Simpson and Barbra C. Keck and each of them singly, his or her true and lawful attorneys-in-fact and agents,Gerard Michel as attorney-in-fact, with full power of substitution, and resubstitution, for him or her and in his or her name, place and stead, in any and all capacities, to sign any and all amendments (includingand post-effective amendments)amendments to this registration statement, and any and all additional registration statements pursuant to Rule 462(b) of the Securities Act and to file the same, with all exhibits thereto and all other documents in connection therewith, with the SEC, granting unto each said attorney-in-factSecurities and agents full power and authority to do and perform each and every act in person,Exchange Commission, hereby ratifying and confirming all that said attorneys-in-fact and agentsattorney-in-fact, or either of them or their, his or her substitute or substitutes, may lawfully do or cause to be done by virtue hereof.thereof.

Pursuant to the requirements of the Securities Act of 1933, this Registration Statement on Form S-3registration statement has been signed by the following persons in the capacities and on the dates indicated.

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EXHIBIT INDEX

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