These results demonstrated that B56γ silencing could aggravate the migratory and invasive hepatocarcinogenesis phenotype in HBV‐related HCC cells, both in vitro and in vivo, via targeting dephosphorylation regulation of the p‐AKTThr308/Ser473‐MMP2/9 pathway. This evidence concerns the gene PPP2R5C and hepatocellular carcinoma.