As filed with the Securities and Exchange Commission on November 29, 2018October 6, 2021

Registration No. 333-227970333-                    

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

Amendment No. 1 toFORM Form S-3

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

Delcath Systems, Inc.DELCATH SYSTEMS, INC.

(Exact name of registrant as specified in its charter)Name Of Registrant As Specified In Its Charter)

1633 Broadway,

Suite 22C

New York, New York 10019

(212) 489-2100

(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)

Jennifer K. Simpson

President andGerard Michel

Chief Executive Officer

Delcath Systems, Inc.

1633 Broadway,

Suite 22C

New York, New York 10019

(212) 489-2100

(Name, address, including zip code, and telephone number, including area code, of agent for service)

Copies of all communications, including communications sent to agent for service, should be sentCopy to:

Jolie Kahn,Veronica Montagna, Esq.

Wexler, Burkhart, HirschbergMcCarter & UngerEnglish, LLP

377 Oak100 Mulberry Street, Four Gateway Center

Garden City, NY 11530Newark, New Jersey 07102

(973) (516) 222-2230639-7948

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

As soon as practicable afterIf the only securities being registered on this Registration Statement becomes effective andForm are being offered pursuant to be sold.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.  ☒

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, of 1933, 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 filedthereto that shall become effective upon filing with the Commission pursuant to Rule 462(d)462(e) under the Securities Act, check the following box and listbox.  ☐

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, registration statement number ofcheck the earlier effective registration statement for the same offering.following box.   ☐

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

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 information in this prospectus is not complete and may be changed. A registration statement relating to these securities has been filed with the Securities and Exchange Commission. These securities may not be sold until the registration statement filed with the Securities and Exchange Commission is effective. This preliminary prospectus is not an offer to sell nor does it seek an offerthese securities, and we are not soliciting offers to buy these securities, in any state or other jurisdiction where the offer or sale is not permitted.

Subject to Completion, dated November 29, 2018.

SUBJECT TO COMPLETION, PRELIMINARY PROSPECTUS DATED OCTOBER 6, 2021

$100,000,000

Up to 638,199 Shares of Common Stock

Preferred Stock

Debt Securities

Depositary Shares

Warrants

Units Offered by the Selling Stockholders

We mayThis prospectus relates to the offer and sell up to $100,000,000 in the aggregate of the securities identified aboveresale, from time to time, by the selling stockholders named under the heading “Selling Stockholders” in onethis prospectus, or more offerings. Thistheir 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 providesdoes not mean that the Selling Stockholders will offer or sell 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 with a general descriptionshould 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.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 commissions in this offering.

Each time we offerWe 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 sell securities,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 provide a supplementreceive, upon issuance of the Common Stock to this prospectus that contains specific information about the offeringSelling Stockholders $1,278 upon exercise of the Warrant, the outstanding principal amount of the Loan will be reduced by $3 million and the amounts, prices8% senior secured promissory notes will no longer be outstanding. See “The Offering” and terms“Use of the securities. TheProceeds” for more details.

A prospectus supplement may also add, update, or change information contained in this prospectus with respect to that offering.prospectus. You should carefully read this prospectus, any applicable prospectus supplement, and the information incorporated by reference in this prospectus and any applicable prospectus supplement before you invest in any ofmake your investment decision.

Our Common Stock is traded on The NASDAQ Capital Market under the symbol “DCTH.” On October 4, 2021, the closing price for our securities.

We may offer and sell the securities described in this prospectus and any prospectus supplement to or through one or more underwriters, dealers and agents, or directly to purchasers, or through a combination of these methods. If any underwriters, dealers or agentsCommon Stock, as reported on The NASDAQ Capital Market, was $9.58 per share. Our principal executive offices are involved in the sale of any of the securities, their names and any applicable purchase price, fee, commission or discount arrangement between or among them will be set forth, or will be calculable from the information set forth, in the applicable prospectus supplement. See the sections of this prospectus entitled “About this Prospectus” and “Plan of Distribution” for more information. No securities may be sold without delivery of this prospectus and the applicable prospectus supplement describing the method and terms of the offering of such securities.located at 1633 Broadway, Suite 22C, New York, New York 10019.

INVESTING IN OUR SECURITIES INVOLVES RISKS. SEE THEInvesting in our Common Stock involves a high degree of risk. You should read carefully the risks and uncertainties that are described in (i) the “RISK FACTORSRisk Factors” ON PAGE 5 OF THIS PROSPECTUS AND ANY SIMILAR SECTION CONTAINED IN THE APPLICABLE PROSPECTUS SUPPLEMENT CONCERNING FACTORS YOU SHOULD CONSIDER BEFORE INVESTING IN OUR SECURITIES.

Our common stock tradessection beginning on page 12 of this prospectus, (ii) the OTCQB“Risk Factors” section of any applicable prospectus supplement or amendment, and (iii) under the symbol “DCTH”. The closing sale price on the OTCQB on November 21, 2018, was $0.49 per share.

Neither“Risk Factors” or similar headings in our periodic reports and other documents filed with the Securities and Exchange Commission (the “SEC”) that are incorporated by reference into this prospectus.

Neither the SEC nor any state securities commission has approved or disapproved of these securities or passed upon the adequacydetermined if this prospectus is truthful or accuracy of this prospectus.complete. Any representation to the contrary is a criminal offense.

The date of this prospectus is        , 2018.2021.

TABLE OF CONTENTS

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 U.S. Securities and Exchange Commission, or the SEC, using a “shelf”shelf registration process. By using a shelfUnder this registration statement, wethe Selling Stockholders may sell securitiesCommon Stock from time to time and in one or more offerings up to a total dollar amount of $100,000,000 as described in this prospectus. This prospectus omits some of the information contained in the registration statement, and reference is made to 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 description of our Common Stock as well as other information you should know before investing in our Common Stock. Each time that wethe Selling Stockholders offer and sell securities,our Common Stock hereby, we will provide aone or more prospectus supplement to this prospectussupplements or amendments that containswill contain specific information about the securities being offered and soldterms of that specific offering of our Common Stock and the specific terms of that offering. Wemanner in which it may also authorize one or more free writing prospectuses to be provided to you that may contain material information relating to these offerings.offered. The prospectus supplement or free writing prospectusamendment 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 respect to that offering. If there is any inconsistency between the informationstatements made in this prospectus, and the applicablestatements made in this prospectus supplementwill be deemed modified or free writing prospectus, you should rely onsuperseded by those made in the prospectus supplement or free writing prospectus, as applicable. Before purchasing any securities, youamendment. You should carefully read both this prospectus and the applicable prospectus supplement (and any applicable free writing prospectuses),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 More Information;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.

We have not authorized anyone to provide you with any information or to make any representations other than those containedAs used in this prospectus, any applicable prospectus supplement“Delcath,” “the Company,” “we,” “our,” or any free writing prospectuses prepared by or on behalf of us or to which we have referred you. We take no responsibility for,“us” mean Delcath Systems, Inc. and can provide no assurance asits wholly owned subsidiaries. The term “Selling Stockholders” refers, collectively, to the reliability of, any other information that others may give you. We will not make an offer to sell these securities in any jurisdiction whereselling stockholders named under the offer or sale is not permitted. You should assume that the information appearingheading “Selling Stockholders” in this prospectus

PROSPECTUS SUMMARY

This prospectus summary highlights certain information about us and the applicable prospectus supplement to this prospectus is accurate only as of the date on its respective cover, that theselected information appearingcontained elsewhere in any applicable free writing prospectus is accurate only as of the date of that free writing prospectus, and that any informationor incorporated by reference into this prospectus. This prospectus summary is accurate only asnot complete and does not contain all of the dateinformation that you should consider before making an investment decision. For a more complete understanding of the document incorporated by reference, unless we indicate otherwise. Our business, financial condition, results of operationsCompany, you should read and prospects may have changed since those dates. This prospectus incorporates by reference, and any prospectus supplement or free writing prospectus may contain and incorporate by reference, market data and industry statistics and forecasts that are based on independent industry publications and other publicly available information. Although we believe these sources are reliable, we do not guaranteeconsider carefully the accuracy or completeness of thismore detailed information and we have not independently verified this information. In addition, the market and industry data and forecasts that may be included or incorporated by reference in this prospectus any prospectus supplement or any applicable free writing prospectus may involve estimates, assumptions and other risks and uncertainties and are subject to change based on various factors, including those discussed under the heading “Risk Factors” contained in this prospectus, the applicable prospectus supplement and any applicable free writing prospectus, and under similar headings in other documents that are incorporated by reference into this prospectus. Accordingly, investors should not place undue reliance on this information.

When we refer to “Delcath,” “we,” “our,” “us” and the “Company” in this prospectus, we mean Delcath Systems, Inc., and its consolidated subsidiaries, unless otherwise specified. When we refer to “you,” we mean the potential holders of the applicable series of securities.

WHERE YOU CAN FIND MORE INFORMATION; INCORPORATION BY REFERENCE

Available Information

Our web site address is http://www.delcath.com/ . The information on our web site, however, is not, and should not be deemed to be, a part of this prospectus.

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

The directionWe are currently reviewing the incidence, unmet need, available efficacy data and focusdevelopment requirements for a broad set of our CDP for CHEMOSAT and Melphalan/HDS is informed by prior clinical development conducted between 2004and 2010, non-clinical, commercial CHEMOSAT cases performed on patients in Europe, and prior regulatory experience with the FDA. Experience gained from this research, development, early European commercial and United States regulatory activity has led to the implementation of several safety improvements to our product and the associated medical procedure.

Currently there are few effective treatment options for certainliver cancers in order to select a portfolio of indications which will maximize the liver. Traditional treatment options include surgery, chemotherapy, liver transplant, radiation therapy, interventional radiology techniques, and isolated hepatic perfusion.value of the HEPZATO platform. This may result in a restart of the ALIGN Trial. We believe that CHEMOSATthe disease states we are investigating and Melphalan/HDS representsintend 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 potentially important advancementpreliminary 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 regional therapythe ITT population, the lower bound of which exceeded the upper bound of the predefined success criteria (8.3%) for the primary liver cancerORR 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), 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 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. We believeFDA 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 CHEMOSATwe 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 Melphalan/HDSpromulgated 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 uniquely positioned to treathighly complex and touches every aspect of product development, manufacturing production, distribution, and post marketing evaluation. As a result of the entire liver either as a standalone therapy or as a complement to other therapies.worldwide COVID-19 pandemic, on April 17, 2020, the European

Cancers inParliament adopted the Liver—A Significant Unmet Need

CancersEuropean Commission’s proposal to postpone the implementation of the liver remain a major unmet medical need globally. AccordingMDR (EU) 2017/745 by 12 months. This urgently drafted proposal to delay the MDR is in response to the American Cancer Society’s (ACS) Cancer Facts & Figures 2017 report, cancerexceptional 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 second leading cause of death in the United States, with an estimated 600,920 deaths and 1,688,780 new cases expected to be diagnosed in 2017. Cancer is oneMDR regulatory changes will impact our business at this time, though implementation of the leading causesmedical device legislation may adversely affect our business, financial condition and results of death worldwide, accounting for approximately 8.2 million deathsoperations or restrict our operations.

Due to COVID-related delays experienced by the medical device industry and 14.1 million new casesNotified 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 2012 according to GLOBOCAN. The financial burden of cancer is enormous for patients, their familiesEurope, accordingly, as Delcath and society. The Agency for Healthcare Quality and Research estimates thatour Notified Body work closely together through the direct medical costs (total of all healthcare expenditures) for cancer in the U.S. in 2014 was $87.8 billion. The liver is often the life-limiting organ for cancer patients and one of the leading causes of cancer death. Patient prognosis is generally poor once cancer has spread to the liver.certification process.

Liver Cancers—Incidence and Mortality

There are two types of liver cancers: primary liver cancer and metastatic liver disease. Primary liver cancer (hepatocellular carcinoma or HCC, including intrahepatic bile duct cancers or ICC) originates in the liver or biliary tissue and is particularly prevalent in populations where the primary risk factors for thedisease, suchas hepatitis-B, hepatitis-C, high levels of alcohol consumption, aflatoxin, cigarette smoking and exposure to industrial pollutants, are present. Metastatic liver disease, also called liver metastasis, or secondary liver cancer, is characterized by microscopic cancer cell clusters that detach from the primary site of disease and travel via the blood stream and lymphatic system into the liver, where they grow into new tumors. These metastases often continue to grow even after the primary cancer in another part of the body has been removed. Given the vital biological functions of the liver, including processing nutrients from food and filtering toxins from the blood, it is not uncommon for metastases to settle in the liver. In many cases patients die not as a result of their primary cancer, but from the tumors that metastasize to their liver. In the United States, metastatic liver disease is more prevalent than primary liver cancer.

Ocular Melanoma

Ocular melanoma is one of the cancer histologies with a high likelihood of metastasizing to the liver. Based on third party research conducted in 2016, we estimate that up to 4,700 cases of ocular melanoma are diagnosed in the United States and Europe annually, and that approximately 55% of these patients will develop metastatic disease. Of metastatic cases of ocular melanoma, we estimate that approximately 90% of patients will develop liver involvement. Once ocular melanoma has spread to the liver, current evidence suggests median overall survival for these patients is generally six to eight months. Currently there is no standard of care (SOC) for patients with ocular melanoma liver metastases. According to our 2016 research, we estimate that approximately 2,000 patients with ocular melanoma liver metastases in the United States and Europe may be eligible for treatment with the Melphalan/HDS.

Intrahepatic Cholangiocarcinoma

Hepatobiliary cancers include hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), and are among the most prevalent and lethal forms of cancer. According to GLOBOCAN, an estimated 78,500 new cases of hepatobiliary cancers are diagnosed in the United States and Europe annually. According to the ACS, approximately 40,710 new cases of these cancers were expected to be diagnosed in the United States in 2017.

ICC is the second most common primary liver tumor and accounts for 3% of all gastrointestinal cancers and 15% of hepatobiliary cases diagnosed in the United States and Europe annually. We believe that 90% of ICC patients are not candidates for surgical resection, andthat approximately 20-30% ofthese may be candidates for certain focal interventions. We estimate that approximately 9,300 ICC patients in the United States and Europe annually could be candidates for treatment with Melphalan/HDS, which we believe represents a significant market opportunity.

According to the ACS, the overall five-year survival rate for hepatobiliary cancers in the United States is approximately 18%. For patient diagnosed with a localized stage of disease, theACS estimates 5-year survival at 31%. The ACSestimates that 5-year survival for all cancers is 68%.

We expectDESCRIPTION OF THE TRANSACTIONS

Term Loan from Avenue Venture Opportunities Fund, L.P.

On August 6, 2021, we entered into a Loan and Security Agreement and Supplement to Loan and Security Agreement (together, the “Loan Agreement”) with Avenue Venture Opportunities Fund, L.P. (the “Lender,” or “Avenue Capital”) for a term loan in an aggregate principal amount of up to $20,000,000 (the “Loan”). The Loan bears interest at an annual rate equal to the greater of (a) the sum of 7.70% plus the prime rate as reported in The Wall Street Journal and (b) 10.95%. The Loan is secured by a security interest in all of the Company’s assets. The Loan maturity date is August 1, 2024.

At closing, the Lender funded the initial $15,000,000 tranche of the Loan (“Tranche 1”), including $4,000,000 which has been funded into a restricted account and will be released upon achievement of (a)(x) positive FOCUS trial efficacy per the trial’s predefined Statistical Analysis Plan (SAP) (specifically the Overall Response Rate exceeds the pre-specified threshold for success defined in the SAP by a statistically significant amount); and (y) based on data contained within the FOCUS trial database and appropriate for use with the U.S. Food and Drug Administration, safety and tolerability among FOCUS trial participants is within the range of currently approved and commonly used cytotoxic chemotherapeutic agents; and (b) raising subsequent net equity proceeds of at least $20,000,000. The Company may request an additional $5,000,000 principal amount (“Tranche 2”) from the Lender between October 1, 2022 and December 31, 2022, with funding of Tranche 2 subject to approval of Avenue Capital’s Investment Committee.

Up to $3,000,000 of the principal amount of the Loan outstanding may be converted (the “Loan Conversion”), at the option of the Lender, into shares of the Company’s common stock at a conversion price of $11.98 per share. The Lender’s right to exercise the Loan Conversion is subject to the Beneficial Ownership Limitation set forth in the Warrant discussed below.

In connection with the Loan, on August 6, 2021, the Company issued to the Lender a warrant (the “Warrant”) to purchase an Applicable Number of shares of Common Stock at an exercise price per share equal to $0.01, which Warrant is exercisable until August 31, 2026. “Applicable Number” means (x) 127,755 shares of Common Stock as of the date the Warrant was issued plus (y) as of the funding date of Tranche 2, if at all, (A) 8.50% of the funded Tranche 2 multiplied by (B) the five-day volume weighted average price per share of Common Stock, determined as of the end of trading on the last trading day before the funding of Tranche 2. The Warrant may not be exercised by the Lender or other holder thereof (the “Holder”) to the extent that after giving effect to the issuance of shares of Common Stock after the exercise of the Warrant, the Holder, together with its affiliates, would beneficially own in excess of 4.99% of the number of shares of Common Stock outstanding immediately after giving effect to the issuance of shares of Common Stock issuable upon exercise of the Warrant (the “Beneficial Ownership Limitation”). The Holder, upon notice to the Company, may increase or decrease the Beneficial Ownership Limitation provided that the proceedsBeneficial Ownership Limitation in no event exceeds 9.99% of these offeringsthe number of shares of Common Stock outstanding immediately after giving effect to the issuance of shares of Common Stock upon exercise of the Warrant.

The Loan Agreement requires that the Company prepare and file with the SEC a registration statement on Form S-3 to register all of the shares of Common Stock issuable upon the exercise of the Loan Conversion and the Warrant. It is not possible to determine if Tranche 2 or any portion thereof will ever be sufficientfunded and, therefore, it is not possible to allow usdetermine the Applicable Number of shares of Common Stock issuable upon exercise of the Warrant after the funding of Tranche 2. Accordingly, the shares of Common Stock registered hereunder include the 127,755 shares that are now available for issuance upon an exercise of the Warrant. If and at such time that Tranche 2 of the Loan is funded, the Company will register the additional shares of Common Stock that will become available for issuance upon an exercise of the Warrant.

Rosalind Convertible Notes

On June 6, 2019, the Company entered into a note purchase agreement with Rosalind Opportunities Fund I L.P. and Rosalind Master Fund L.P. (together, “Rosalind”), pursuant to continuewhich Rosalind agreed to transfer and

surrender to the Company for cancellation, warrants to purchase 5,605 shares of our ongoing clinical trial programs, however, weCommon 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 an aggregate principal amount of $2,000,000 secured by a security interest in all assets of the Company and maturing on July 15, 2021, in full payment and satisfaction of the purchase price for the Series D Warrants and Pre-Funded Series D Warrants.

The transactions contemplated by the note purchase agreement were effective and the Convertible Notes were issued on July 15, 2019, upon the closing of the Company’s July 2019 private placement of Series E convertible preferred stock, par value $0.01 per share (“Series E Preferred Stock) and warrants to purchase shares of Common Stock, to various investors, including Rosalind (the “July 2019 Private Placement”). Immediately following the closing of the July 2019 Private Placement, the Convertible Notes were amended, pursuant to a note amending agreement dated as of July 15, 2019 between the Company and Rosalind to provide that the outstanding principal amount of the Convertible Notes and any accrued and unpaid interest thereon are subjectconvertible, at the option of the holder of the Convertible Notes, into shares of Series E Preferred Stock at the price of $1,500.

On August 6, 2021, in connection with the closing of the term loan between the Company and Avenue Capital, the Company and Rosalind executed a Second Note Amending Agreement to substantial risks that could require usfurther amend the Convertible Notes by (a) reducing the conversion price of the notes to obtain additional funding$1,198 per share of Series E Preferred Stock; and (b) extending the maturity date of the Convertible Notes to October 30, 2024. In addition, in order to achieve these objectives. See “Risk Factors.” We may need substantial additional capitalinduce Avenue Capital to provide the Loan, Rosalind agreed to subordinate (a) all of the Company’s indebtedness and obligations to the holders of the Convertible Notes and (b) all of the Convertible Note holders’ security interest in the future, which could cause dilutionCompany’s assets, to our existing shareholders, restrict our operations or require usthe Loan and Avenue Capital’s security interest in the Company’s assets.

The shares of Common Stock registered hereunder include the shares of Common Stock issuable to relinquish rights,Rosalind upon any conversion of Series E Preferred Stock held by Rosalind resulting from the conversion of Convertible Notes.

Common Stock Held by Director Roger G. Stoll and ifChief Operating Officer John Purpura

In July 2019, Roger G. Stoll, the Chair of the Company’s Board of Directors, participated in the July 2019 Private Placement and, in connection therewith, was issued 93 shares of Series E Preferred Stock and a warrant to purchase 4,038 shares of Common Stock. The Series E Preferred Stock and related warrant were issued to Mr. Stoll in lieu of cash compensation owed to him for his services as a director of the Company in 2018. In May 2020, Mr. Stoll exercised his right to convert his Series E Preferred Stock to Common Stock and, as a result thereof, was issued 9,300 unregistered shares of Common Stock. The shares of Common Stock registered hereunder include the 9,300 unregistered shares of Common Stock held by Mr. Stoll.

In July 2019, John Purpura, the Company’s current Chief Operating Officer, participated in the July 2019 Private Placement and, in connection therewith, was issued 65 shares of Series E Preferred Stock and a warrant to purchase 1,083,333 shares of Common Stock. The Series E Preferred Stock and related warrant were issued to Mr. Purpura in lieu of cash compensation owed to him for his services as an officer of the Company in 2018. In May 2020, Mr. Purpura exercised his right to convert his Series E Preferred Stock to Common Stock and, as a result thereof, was issued 6,500 unregistered shares of Common Stock. In addition, in May 2020, Mr. Purpura received an additional capital is not available, we may have6,613 unregistered shares of Common Stock in lieu of a cash bonus due to delay, reduce or cease operations.him for his services as an officer of the Company in 2019. The shares of Common Stock registered hereunder include the aggregate 13,113 unregistered shares of Common Stock held by Mr. Purpura.

DESCRIPTION OF CAPITAL STOCK

Authorized Capital Stock

The following is a description of the material terms of our capital stock is not complete and may not contain all the information you should consider before investingincluded in our capital stock.Amended and Restated Certificate of Incorporation, as amended (our “Certificate of Incorporation”), and our Amended and Restated By-Laws (our “By-Laws”). This description is summarized from, and qualified in its entirety by reference to, our certificate of incorporation, which has been publicly filed with the SEC. See “Where You Can Find More Information; Incorporation by Reference.”

DESCRIPTION OF CAPITAL STOCK AND RECENT TRANSACTIONS

The following description of our common stock and preferred stock 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 ourAmended 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 ourAmended 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

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 November 21, 2018,October 5, 2021, there were 2,475,000 shares of the Company’s common stock reserved under the Delcath Systems, Inc. 2020 Omnibus Equity Incentive Plan, of which 1,255,250 shares remained available to be issued. As of October 5, 2021, we had 9,022,952(a) 3,894,498 shares of common stock outstanding and 85 shares of preferred stock outstanding. As of November 21, 2018, we had 66.9 million shares issuable upon the exercise of outstanding warrants, including (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 Avenue Venture Opportunities Fund, LP at a weighted average exercise price of $2.99$9.27 per share and (b) 1,718,249 shares of common stock issuable upon the exercise of outstanding options with a weighted average exercise price of $11.69 per 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.

Listing

Market Information. Our common stock is quotedtraded on the OTCQBNasdaq 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.

AsIn 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 dateState of this prospectus, we have designatedDelaware, or the following seriesDelaware 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:stock as shares of Series AE 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 BE-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 CE-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 DE-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. None

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 Series A, Series B or Series Ccommon stock. Any such dividends that are not paid to the holders of Preferred Stock are issued and outstanding. 85will increase the Stated Value. No other dividends will be paid on shares of Series DPreferred Stock.

Liquidation rights. Upon any liquidation of the Company, the holders of Preferred Stock are issuedwill be entitled to receive out of the assets of the Company an amount equal to the Stated Value plus any accrued and outstanding asunpaid dividends thereon for each share of November 21, 2018. NonePreferred Stock before any distribution or payment will be made to the holders of the common stock.

Anti-Takeover Effects 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 Series A, Series B, Series C or Series Dpreferred stock is likely to be registered under this prospectus.

Anti-Takeover Effectssenior 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 Delaware Lawdiscouraging unsolicited acquisition proposals, thus adversely affecting the market price of our common stock.

We are subject to the provisions of Section 203 of the Delaware General Corporation Law. Under Section 203, we would generally be prohibitedLaw, which prohibits Delaware corporations from engaging in any business combinationa wide range of specified transactions with any interested stockholder, for a period of three years following the time that this stockholder became an interested stockholder unless:

THE OFFERING

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 SEC on March 31, 2021, which are incorporated in this prospectus by reference in their entirety. Additional risk factors that you 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 the 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 of the risks or uncertainties described in this prospectus, any applicable prospectus supplement or amendment, or the documents incorporated by reference herein actually occur, our business, financial condition, results of operations 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, and the documents incorporated by reference herein, contain, or will contain, “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 “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 future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to 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 interested stockholderSelling Stockholders hereunder. However, assuming (i) the conversion of all of the benefitSeries 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 any loans, advances, guarantees, pledgesthe 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 8% senior secured promissory notes will be no longer be outstanding. We have agreed to pay all costs, expenses and fees relating to the registration of the shares of Common Stock covered by this prospectus.

SELLING STOCKHOLDERS

The Selling Stockholders, or each of their donees, pledgees, assignees, transferees or other financial benefits provided by or through the corporation.

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 Rosalind Maser Fund L.P. (“Rosalind”), pursuant to which Steven Salamon and Gil Aharon, who are principals of Rosalind, have been appointed as directors of the debt securitiesCompany’s board of Directors. Certain shares of Common Stock registered for resale hereunder are also held by Roger G. Stoll, who is the Chairman of the Board of Directors of the Company and John Purpura, who serves as the indentures (includingChief Operating Officer of the Company. Except as a result of the term loan transaction with Avenue Capital described herein under the heading “Description of the Transactions,” Avenue Capital has not held any amendmentsposition or supplements we may enter intooffice with us or any of our predecessors or affiliates within the last three years and has not had a material relationship with us or any of our predecessors or affiliates within the past three years.

PLAN OF DISTRIBUTION

We are registering the shares 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 the holders of the shares of Common Stock from time to time whichafter 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 permitted undersold through underwriters or broker-dealers, the debt securities or an indenture).

Unless otherwise specified in a prospectus supplement, the debt securitiesSelling Stockholders will be direct unsecured obligationsresponsible 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 at fixed prices, at prevailing market prices at the time of the Company. Any debt securities designated as senior will rank equally with anysale, at varying prices determined at the time of our other senior and unsubordinated debt. Any debt securities designated as subordinated will be subordinate and junior in right of payment to any senior indebtedness. Theresale, or at negotiated prices. These sales may be subordinated debt securities that are senioreffected in transactions, which may involve crosses or junior to other series of subordinated debt securities.

block transactions. The applicable prospectus supplement will set forth the termsSelling Stockholders may use any one or more of the debt securities or any series thereof, including, if applicable:following methods when selling shares of Common Stock:

deposit agreement will automatically terminate if (a) all outstanding depositary shares thereunder shall have been redeemed, (b) there shall have been a final distribution in respect of the related preferred stock in connection with any liquidation, dissolutionor winding-up of Delcath and such distribution shall have been distributed to the holders of depositary receipts evidencing the depositary shares representing such preferred stock or (c) each share of the related preferred stock shall have been converted into stock of Delcath not so represented by depositary shares.

Charges of Depositary

We will pay all transfer and other taxes and governmental charges arising solely from the existence of the depositary arrangements. We will pay charges of the depositary in connection with the initial deposit of the preferred stock and initial issuance of the depositary shares, and redemption of the preferred stock and all withdrawals of preferred stock by owners of depositary shares. Holders of depositary receipts will pay transfer, income and other taxes and governmental charges and certain other charges as are provided in the deposit agreement to be for their accounts. In certain circumstances, the depositarycourse of hedging in positions they assume. The Selling Stockholders may refuse to transfer depositaryalso sell shares may withhold dividendsshort and distributions and sell the depositary shares evidenced by such depositary receipt if such charges are not paid. The applicable prospectus supplement will include information with respect to fees and charges, if any, in connection with the deposit or substitution of the underlying securities, the receipt and distribution of dividends, theshort sale or exercise of rights, the withdrawal of the underlying security, and the transferring, splitting or grouping of receipts. The applicable prospectus supplement will also include information with respect to the right to collect the fees and charges, if any, against dividends received and deposited securities.

Miscellaneous

The depositary will forward to the holders of depositary receipts all notices, reports and proxy soliciting material from us which are delivered to the depositary and which we are required to furnish to the holders of the preferred stock. In addition, the depositary will make available for inspection by holders of depositary receipts at the principal office of the depositary, and at such other places as it may from time to time deem advisable, any notices, reports and proxy soliciting material received from us which are received by the depositary as the holder of preferred stock. The applicable prospectus supplement will include information about the rights, if any, of holders of receipts to inspect the transfer books of the depositary and the list of holders of receipts.

Neither the depositary nor Delcath assumes any obligation or will be subject to any liability under the deposit agreement to holders of depositary receipts other than for its negligence or willful misconduct. Neither the depositary nor Delcath will be liable if it is prevented or delayed by law or any circumstance beyond its control in performing its obligations under the deposit agreement. The obligations of Delcath and the depositary under the deposit agreement will be limited to performance in good faith of their duties thereunder, and they will not be obligated to prosecute or defend any legal proceeding in respect of any depositary shares or preferred stock unless satisfactory indemnity is furnished. Delcath and the depositary may rely on written advice of counsel or accountants, on information provided by holders of the depositary receipts or other persons believed in good faith to be competent to give such information and on documents believed to be genuine and to have been signed or presented by the proper party or parties.

In the event the depositary shall receive conflicting claims, requests or instructions from any holders of depositary receipts, on the one hand, and us, on the other hand, the depositary shall be entitled to act on such claims, requests or instructions received from us.

Resignation and Removal of Depositary

The depositary may resign at any time by delivering to us notice of its election to do so, and we may at any time remove the depositary, any such resignation or removal to take effect upon the appointment of a successor depositary and its acceptance of such appointment. Such successor depositary must be appointed within 60 daysplace after delivery of the notice for resignation or removal and must be a bank or trust company having its principal office in the United States and having a combined capital and surplus of at least $100,000,000.

The Selling Stockholders and 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 limit the timing of purchases and sales of any of the shares of Common Stock by the Selling Stockholders and any other participating person. Regulation M may also restrict the ability of any person engaged in the registration statementdistribution of the shares of Common Stock to engage in market-making activities with respect to the shares. All of the foregoing may affect the marketability of the shares and the ability of any person or entity to engage in market-making activities with respect to the shares.

LEGAL MATTERS

The validity of the shares of Common Stock to be offered for resale by the Selling Stockholder under this prospectus will be passed upon for us by McCarter & English, LLP, Newark, New Jersey.

EXPERTS

The consolidated financial statements as of December 31, 2020 and 2019 and for each of the two years in the period ended December 31, 2020 incorporated by reference in this prospectus have been so incorporated by reference in reliance uponon the reportsreport of Grant ThorntonMarcum, LLP, an independent registered public accountants, uponaccounting firm, incorporated herein by reference, given on the authority of said firm as experts in accountingauditing and auditing.accounting.

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 PROSPECTUS

Item 14.Other Expenses of Issuance and Distribution

The following is an estimate of thetable sets forth various expenses (all of which are to be paidbeing borne by the registrant) that we may incurCompany in connection with the sale and distribution of the securities being registered hereby.registered. All of the amounts shown are estimates except for the Securities and Exchange Commission Registration Fee.

breach of his or her fiduciary duty as a director, provided that such provision shall not eliminate or limitexcept where the liability of a director (i) for any breach of the director’sbreached his duty of loyalty, failed to the corporation or its stockholders, (ii) for acts or omissions notact in good faith, or which involveengaged in intentional misconduct or a knowing violation of law, (iii) under Section 174authorized the payment of a dividend or approved a stock repurchase in violation of the DGCL or (iv) for any transaction from which the director derivedobtained an improper personal benefit.

Any underwriting agreementArticle 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 distribution agreement that the registrant enters intopaid by such person in connection with any underwritersproceeding arising from the fact that such person is or agents involvedwas an officer or director of our company, and to advance expenses as incurred by or on behalf of such person in the offering or saleconnection therewith.

The indemnification rights set forth above shall not be exclusive of any securities registered herebyother right which an indemnified person may require such underwritershave or dealershereafter 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 provide coverage (1) to indemnify the registrant, some or all of itsour directors and officers against loss rising from claims made by reason of breach of duty or other wrongful act and its controlling persons, if any, for specified liabilities, which(2) to us with respect to indemnification payments that we may include liabilities under the Securities Act of 1933, as amended.

The registrant’s Amended and Restated Certificate of Incorporation and Amended andRestated By-laws provide that it shall indemnify itsmake to such directors and officers to the fullest extent authorized or permitted by law, and such right to indemnification shall continue as to a person who has ceased to be a director or officer of the registrant and shall inure to the benefit of his or her heirs, executors and personal and legal representatives. The registrant’s bylaws further provide that the registrant shall pay the expenses (including attorneys’ fees) incurred by an indemnitee in defending any proceeding in advance of its final disposition under certain circumstances.officers.

Item 16.Exhibits

(a)

Item 16.

Exhibits.

A list of exhibits filed with this registration statementon Form S-3 is set forth on the Exhibit Index and is incorporated herein by reference.

Item 17.Undertakings

The Registrant hereby undertakes:

(a) The undersigned registrant hereby undertakes:

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

(ii) To 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 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.

therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering 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.

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

(A)(i) Each prospectus filed by the 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

(B)(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 sectionSection 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 initial bona fide offering thereof. Provided,thereof; provided, however,, that no statement made in a registration 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.

(6) That, for the purpose of determining liability of the registrant under the Securities Act of 1933 to any purchaser in the initial distribution of the securities:

The undersigned registrant 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;

EXHIBIT INDEXExhibit Index

II-5

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 FormS-3 and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of New York, State of New York, on November 29, 2018.October 6, 2021.

POWER OF ATTORNEY

KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Gerard Michel as attorney-in-fact, with power of substitution, in any and all capacities, to sign any and all amendments and post-effective amendments to this registration statement, and to file the same, with all exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, hereby ratifying and confirming all that said attorney-in-fact, or his substitute or substitutes, may do or cause to be done by virtue thereof.

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

Each person whose signature appears below constitutes and appoints Jennifer K. Simpson and Barbra C. Keck and each of them singly, his or her trueand lawful attorneys-in-fact and agents, 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 (including post-effective 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 untoeach said attorney-in-fact and agents full power and authority to do and perform each and every act in person, hereby ratifying and confirming allthat said attorneys-in-fact and agents or either of them or their, his or her substitute or substitutes may lawfully do or cause to be done by virtue hereof.