Treatment of hepatocellular carcinoma (HCC) cells with the small-molecule EZH2 inhibitors GSK343 or GSK126 was able to upregulate several activating NK cell ligands, such as ULBP1-6, MICA, MICB, PVR and NECTIN2, which led to a significant increase in NK cell-induced cytotoxicity dependent especially on ULBP1 and MICA. This evidence concerns the gene ULBP1 and hepatocellular carcinoma.