PP2A‐B56γ inhibited the p‐AKTThr308/Ser473‐dependent hepatocarcinogenesis via a specific dephosphorylation regulatory mechanism, while the genetic intervention of PPP2R5C function mediated the targeted modulation of p‐AKT‐MMP2/9‐EMT‐mediated HCC cell phenotypes. This evidence concerns the gene AKT1 and hepatocellular carcinoma.