Tumor cells expression of programmed death ligand-1 (PD-L1) is a major mechanism of immune escape and a predictor of therapeutic efficacy of immune checkpoint inhibitors. The expression of PD-L1 is regulated by a variety of mechanisms, among which epigenetic modifications such as DNA methylation, histone modification and non-coding RNA can promote the occurrence, development and drug resistance of tumors by regulating the expression of PD-L1. To clarify its regulation mechanism can bring new ideas for clinical immunotherapy of tumors.