Objective To explore the relationship between X-ray repair cross-complementary group 1(XRCC1) codon 399 polymorphism and genetic susceptibility to hepatocellular carcinoma (HCC). Methods Literatures of case-control studies about XRCC1 codon 399 polymorphism and genetic susceptibility to HCC were retrieved, related information was extracted, and meta-analysis was performed on research findings. Odds ratios (ORs) and 95% confidence interval (95% CI) were calculated using fixed- or random-effects model via heterogeneity test, and the publication bias and sensitivity were evaluated. Results Seven domestic and overseas literatures were enrolled, including 1 342 cases of HCC and 2 207 controls. The combined data analysis indicated that XRCC1 codon 399 Gln/Gln increased risk for HCC (OR=1.41, 95% CI=1.07-1.84), while XRCC1 codon 399 Lys/Gln was not related to risk for HCC. Subgroup analysis revealed that both Lys/Gln and Gln/Gln were related to HCC in areas with high incidence of HCC （OR=1.46, 95% CI 1.07-2.00; OR=1.45, 95% CI 1.09-1.93）. Conclusion XRCC1 codon 399 polymorphism is associated with the susceptibility to HCC.