Abstract:  Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, with the majority of  patients being diagnosed at intermediate to advanced stages, resulting in a poor prognosis. Lactylation, a novel post⁃translational modification (PTM) driven by cellular metabolism, plays a pivotal role in regulating oncogene expression, driving metabolic reprogramming, and shaping the immunosuppressive tumor microenvironment (TME) by modifying histones and key effector proteins. Research has demonstrated that lactylation exhibits significant potential in HCC diagnosis, prognostic assessment, and targeted therapy. The combination of anti⁃lactylation regulation and immunotherapy may further enhance the efficacy of HCC treatment. Lactylation serves not only as a potential biomarker for HCC diagnosis and prognosis prediction, but also provide promising new targets for drug development through its key nodes within the regulatory network. This review summarizes the generation and functions of lactylation, its mechanisms in driving HCC malignant progression, and its potential applications in HCC diagnosis and treatment.

Key words: Hepatocellular carcinoma, Lactylation, Metabolic reprogramming, Tumor microenvironment, Therapeutic target