Hepatocellular carcinoma (HCC) is a highly lethal cancer in which epigenetic dysregulation plays a key role in tumor development and progression. Among epigenetic mechanisms, histone methylation regulates chromatin structure and gene transcription and influences multiple aspects of HCC biology, including tumor proliferation, metastasis, immune modulation, cancer stemness, and therapeutic resistance. In this review, we summarize recent advances in understanding the roles of histone methyltransferases in HCC, focusing on their involvement in tumor proliferation, metastasis, immune regulation, drug resistance, and cancer stem cell maintenance. We also discuss their clinical relevance as potential diagnostic and prognostic biomarkers and highlight emerging therapeutic strategies targeting histone methylation pathways. Collectively, these findings suggest that histone methyltransferases represent promising targets for developing novel epigenetic-based diagnostic and therapeutic approaches for HCC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, and therapeutic cancer vaccines have emerged as a promising immunotherapeutic strategy. These vaccines target tumor-associated antigens such as glypican-3, alpha-fetoprotein, melanoma-associate antigen-1, heat shock protein 70, glutamine synthetase, and TMEM176A/B, which are abnormally expressed in HCC cells and serve as both diagnostic markers and therapeutic targets. Various vaccine platforms—including peptide-based, dendritic cells-based, viral vector-based, and genetic vaccines (DNA/mRNA)—are under investigation for their ability to elicit antigen-specific cytotoxic T cell responses and establish long-term immune memory. Despite promising preclinical and early clinical results, challenges such as the immunosuppressive tumor microenvironment, antigen heterogeneity, and immune evasion mechanisms limit their efficacy. Future strategies focus on combination therapies with immune checkpoint inhibitors, personalized neoantigen vaccines, and advanced delivery technologies. These approaches aim to enhance immunogenicity and clinical outcomes, positioning therapeutic cancer vaccines as a key component of precision oncology in HCC.