XRCC1 genetic polymorphisms could be associated with increased risk of various cancer, includinghepatocellular carcinoma (HCC), the fifth most common cancer. We here conducted a study to explore the roleof selective SNPs of the XRCC1 and XPD genes in the prognosis of HCC. A total of 231 cases were collected, andgenotyping of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn was performedby duplex polymerase-chain-reaction with the confronting-two-pair primer method. Our findings indicatedXRCC1 399Gln/Gln genotype was associated with a significant difference in the median survival time comparedwith patients carrying Arg/Trp and Arg/Arg genotypes, and individuals with XPD 751 Gln/ Gln genotype had asignificantly greater survival time than patients carrying Lys/Lys and Lys/Gln genotypes. The Cox’s regressionanalysis showed individuals carrying XRCC1 399Trp/Trp genotype had 0.55 fold risk of death from HCC thanArg/Arg genotype. Similarly, XPD 751Gln/Gln had a strong decreasein comparison to XPD Lys/Lys carriers withan HR of 0.34. These results suggest that polymorphisms in XRCC1 and XPD may have functional significancein the prognosis of HCC.