In subgroup analysis by hepatitis virus infection status, the results showed that the MDM2 SNP309 polymorphism was associated with increased HCC risk in HCV positive patients (G vs. T: OR = 1.481, 95%CI: 1.245–1.761, P = 0.000; GG vs. TT: OR = 2.198, 95%CI: 1.542–3.134, P = 0.000; TG vs. TT: OR = 1.759, 95%CI: 1.280–2.418, P = 0.001; GG vs. TG+TT: OR = 1.507, 95%CI: 1.147–1.980, P = 0.003; GG+TG vs. TT: OR = 1.926, 95%CI: 1.426–2.601, P = 0.000) but not in HBV positive subjects. This evidence concerns the gene MDM2 and hepatocellular carcinoma.