Abstract: Epigenetic modifications regulate gene expression without altering DNA sequences, thereby affecting cell function and differentiation. Recent studies have shown that epigenetic modifications play crucial roles in immune function regulation, particularly in regulation of T cell differentiation and function. Chimeric antigen receptor T-cell (CAR-T) therapy has achieved great success in treatment of hematological malignancies, but faces significant barriers, including poor infiltration, exhaustion, and short persistence, in treating solid tumors. Epigenetic modifications can enhance CAR-T cell functionality by regulating groups of genes, representing a new strategy for improving CAR-T cell efficacy in solid tumors. We systematically describe mechanisms by which epigenetic modifications regulate CAR-T cell differentiation and function and explore optimization strategies for CAR-T cell epigenetic modification, providing a theoretical basis for enhancing CAR-T cell therapy efficacy in solid tumors.