In the MDM2 SNP309–TP53 R72P interaction analysis, we found that individuals with MDM2 309TT and TP53 Pro/Pro genotype, MDM2 309 TG and TP53 Arg/Pro genotype, and MDM2 309 GG and TP53 Pro/Pro genotype had significantly increased HCC risk compared to those with the reference MDM2 309TT and TP53 Arg/Arg genotype. Here, MDM2 is linked to hepatocellular carcinoma.