In comparison to the reference MDM2 309TT and p53 Arg/Arg genotype, subjects with the MDM2 309TT and TP53 Pro/Pro genotype (OR = 1.996, 95%CI: 1.076–3.700, P = 0.028), MDM2 309 TG and TP53 Arg/Pro genotype (OR = 1.627, 95%CI: 1.110–2.385, P = 0.013), and MDM2 309 GG and TP53 Pro/Pro genotype (OR = 5.237, 95%CI: 2.845–9.639, P = 0.000) present significantly higher risk of developing HCC. Here, MDM2 is linked to hepatocellular carcinoma.