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The noninvasive, nonthermal, nonionizing mechanical mechanism by which it destroys tumor tissues makes it an appealing local therapy option in the treatment of patients with early\u2010stage hepatocellular carcinoma (HCC). In this article, the authors review the current evidence base for histotripsy in HCC and explore its potential role in routine care based on technical, safety, and clinical considerations. They then describe the evidence gaps that remain with respect to histotripsy\u2019s treatment efficacy, comparative effectiveness, and safety relative to established local therapy options including thermal ablation, transarterial chemoembolization and radioembolization, and stereotactic body radiotherapy. Although the current body of evidence supports the technical feasibility, short\u2010term safety, and early local tumor control of histotripsy in the treatment of patients with HCC, standardized response assessments, rigorous prospective evaluations of durable oncologic outcomes, and direct comparisons with existing therapies in well\u2010defined patient populations are still needed before histotripsy can be fully integrated into standard HCC care.<\/jats:p>","DOI":"10.1002\/cncr.70547","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T07:26:33Z","timestamp":1785137193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Where does histotripsy fit into hepatocellular carcinoma care?"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8854-224X","authenticated-orcid":false,"given":"Kelsey S.","family":"Lau\u2010Min","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology Department of Medicine Mass General Brigham Cancer Institute and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7466-098X","authenticated-orcid":false,"given":"Jiping","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology Department of Surgery Mass General Brigham and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Liver Fact Sheet","author":"The Global Cancer Observatory"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31288"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100030\u20101247128"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23478"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2025.10.020"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1109\/tuffc.2004.1308731"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/02656736.2021.1905189"},{"key":"e_1_2_9_9_1","unstructured":"US Food & Drug Administration.Device Classification Under Section 513(f)(2)(De Novo). 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