To predict HCC risk, the best interaction model selected from the six positive SNPs was the four-factor model including ERCC1 rs2298881 -XPC rs1870134-ERCC2 rs238417-ERCC5 rs873601 SNPs, which yielded the highest testing accuracy of 0.6001 and the maximal CV consistency of 10/10 (significant test P = 0.0010, and P for permutation test = 0.0010–0.0020). The gene discussed is ERCC5; the disease is hepatocellular carcinoma.