In summary, the results of the current study demonstrate for the first time that LASS2 exerts a tumor-suppressive effects by interacting with MDM2 and MDMX and promoting p53 ser15 phosphorylation and lys373 acetylation in the different subtypes of hepatoma cells that harbor wild-type and mutant p53, thereby stabilizing p53. This evidence concerns the gene MDM2 and hepatocellular carcinoma.