In conclusion, the present study demonstrated that the epigenetic modifier EZH2 can suppress the expression of immune checkpoint inhibitor PD-L1 by directly upregulating the promoter H3K27me3 levels of CD274 and IRF1 in hepatoma cells and might serve as a potential therapeutic target for combination of cancer immunotherapy for immune-activated HCC. This evidence concerns the gene CD274 and hepatocellular carcinoma.