BACKGROUND DNA base-excision repair genes hOGG1 and XRCC1 play an important role in preserving genetic stability in mammalian cells against any damage caused by different factors. However, it is unclear whether altered expression and function of these DNA repair genes could lead to hepatocellular carcinoma (HCC) susceptibility. OBJECTIVE This study determined the association between polymorphisms of the genes encoding two key proteins of DNA base excision repair (hOGG1 ser326Cys and XRCC1 Arg 280His) and HCC risk. METHODS A total of 350 HCC patients (mean age of 51.1 years) and 400 healthy controls (mean age of 51.4 years) were recruited for analysis of XRCC1 and hOGG1 gene polymorphisms using PCR plus restriction fragment length polymorphism (PCR-RFLP). RESULTS The data showed that the hOGG1 Cys326Cys and Ser326Cys genotypes were associated with increase in HCC risk. In contrast, there was no association between HCC susceptibility and the distribution of XRCC1 His 280 His and Arg280His. However, combination of these two gene polymorphisms (XRCC1-280 Arg and hOGG1-326Cys) is associated with significant induction of HCC risk. In addition, the data also showed that XRCC1 280His polymorphism was associated with HBV infection and HCC family history to increase HCC risk. The hOGG1 326cys genotype was associated with alcohol consumption, tobacco smoke, and HBV infection to increase HCC risk. CONCLUSIONS The data from the current study demonstrated the association of these two DNA repair gene polymorphisms with HCC risk. Future studies will confirm these data before they can be used as a biomarker for assessing HCC risk.