An increased oxidant burden has been implicated in hepatocarcinogenesis, and several antioxidant enzymes counteract potential oxidative damage. So, polymorphisms in the genes encoding antioxidant enzymes may play an important role in the development of hepatocellular carcinoma (HCC). To test this hypothesis, we investigated the association of polymorphisms in antioxidant enzyme genes, including three superoxide dismutases (SODs), catalase (CAT), and glutathione peroxidase (GPx), with HCC in a Chinese population consisting of 434 HCC patients and 480 control subjects. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were estimated by unconditional logistic regression. For the ECSOD Ala40Thr polymorphism, a significant association was observed between this polymorphism and HCC risk in non-hepatitis B virus (HBV) carriers but not in HBV carriers, and individuals with one 40Thr allele (Ala/Thr genotype) (OR = 2.13, 95 % CI = 1.25-3.64, P = 0.006) or at least one 40Thr allele (Ala/Thr and Thr/Thr genotype) (OR = 1.90, 95 % CI = 1.15-3.15, P = 0.012) showed significantly higher risk to HCC, compared with Ala/Ala genotype. No significant associations were observed between three other polymorphisms (MnSOD Ala16Val, CAT-262C/T, GPx Pro198Leu) and HCC susceptibility in both HBV carriers and non-HBV carriers. Furthermore, no other signs of combined effects, except for a combined effect of ECSOD Ala40Thr and MnSOD Val16Ala in non-HBV carriers, were observed for each combination of these four polymorphisms. In conclusion, our results indicate that the antioxidant enzyme gene polymorphisms at least partially contribute to the susceptibility to HCC.