In this study, we demonstrated that IFN-γ significantly induced galectin-9 expression in HCC cells, a change accompanied by EZH2 up-regulation, and that EZH2 indirectly regulated galectin-9 expression by epigenetically repressing miR-22, a regulator of galectin-9 in HCC. Here, LGALS9 is linked to hepatocellular carcinoma.