Our mechanistic studies showed that EZH2 epigenetically silenced IFNγ-induced PD-L1 expression by upregulation of the H3K27me3 levels on the promoters of both CD274 and IRF1. Notably, EZH2 did not affect the activation of IFNγ-STAT1 signaling in hepatoma cells, as analyzed by qPCR and immunoblotting assays. Here, IFNG is linked to hepatocellular carcinoma.