The tumor suppressor protein p53 is a key regulator of cell cycle arrest and apoptosis. Snail protein regulates cancer-associated malignancies. However, the relationship between p53 and Snail proteins in hepatocellular carcinoma (HCC) has not been completely understood. To determine whether Snail and p53 contribute to hepatocarcinogenesis, we analyzed the expression of Snail proteins in p53-overexpressing HCC cells. We found that p53 wild-type (WT) induced the degradation of Snail protein via murine double minute 2-mediated ubiquitination, whereas p53 mutant did not induce Snail degradation. As we expected, only p53WT induced endogenous Snail protein degradation and inhibited tumor cell invasion. These findings contribute to a better understanding of the role of p53 mutation and Snail overexpression as a late event in hepatocarcinogenesis. Structured summary: MINT-7718917: p53 (uniprotkb:P04637) physically interacts (MI:0915) with Snai1 (uniprotkb:O95863) by anti bait coimmunoprecipitation (MI: 0006) MINT-7719877: Snai1 (uniprotkb: O95863) physically interacts (MI: 0915) with ubiquitin (uniprotkb: P62988) by anti tag coimmunoprecipitation (MI: 0007) MINT-7718928: Snai1 (uniprotkb: O95863) physically interacts (MI: 0915) with p53 (uniprotkb: P04637) by anti tag coimmunoprecipitation (MI: 0007) MINT-7718939: Snai1 (uniprotkb: O95863) physically interacts (MI: 0915) with MDM2 (uniprotkb: Q00987) by anti tag coimmunoprecipitation (MI: 0007) (C) 2010 Federation of European Biochemical Societies.