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Natural killer (NK) cells are essential for immune surveillance, yet their quantity and function become significantly compromised during HCC progression, thereby promoting tumour immune escape. This review systematically outlines current NK cell\u2010based immunotherapeutic strategies for HCC, including adoptive NK cell transfer, genetic engineering of NK cells, NK cell inhibitory receptor\u2010targeted therapies, reprogramming of the immunosuppressive HCC microenvironment, cytokine\u2010mediated enhancement of NK cell function, and traditional Chinese medicine\u2010augmented NK cell cytotoxicity. Representing a promising immunotherapeutic paradigm, NK cell\u2010based therapy is rapidly advancing from conventional cell infusion toward more precise modalities, including CAR\u2010NK cells and multifunctional antibody engagers. However, the efficacy of these approaches is frequently curtailed by the immunosuppressive tumour microenvironment and tumour heterogeneity. Given the multifactorial nature of NK cell dysfunction, we highlight that rationally designed combination strategies\u2010integrating genetic engineering, TME reprogramming, and checkpoint blockade\u2010represent the most viable path toward durable clinical responses in HCC.<\/jats:p>","DOI":"10.1111\/imm.70141","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:38:53Z","timestamp":1777369133000},"page":"615-632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Killer Cell\u2010Based Immunotherapy in\n                    <scp>HCC<\/scp>"],"prefix":"10.1111","volume":"178","author":[{"given":"Linlin","family":"Che","sequence":"first","affiliation":[{"name":"Department of Immunology and Pathogenic Biology, School of Integrative Medicine Shanghai University of Traditional Chinese Medicine  Shanghai People's Republic of 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