To investigate whether EZH2 promoted HCC progression by miR-381/SETDB1/AKT pathway in vivo, we knocked down or overexpressed EZH2 in AKT overexpressed Huh7 cells and analyzed the EHZ2, SETDB1 and AKT pathway-related downstream expression by RT-qPCR and ELISA. This evidence concerns the gene SETDB1 and hepatocellular carcinoma.