We aimed to investigate the role of XRCC1 codon 194 (Arg>Trp), 280 (Arg>His), and 399 (Arg>Gln) polymorphisms in response to chemotherapy and the overall survival of gastric cancer patients. A total of 172 patients were recruited for our study between January 2010 and March 2012. Genotyping of the three XRCC1 codons was carried out by restriction fragment length polymorphism polymerase chain reaction. By logistic regression analysis, we found that the Trp/Trp genotype of XRCC1 194 (Arg>Trp) showed a stronger association with complete or partial response to chemotherapy compared to the Arg/Arg genotype, and the adjusted odds ratio (95%CI) was 0.17 (0.05-0.58). Moreover, the Trp/Trp genotype was associated with a higher risk of death than that with the Arg/Arg genotype based on multivariate Cox proportional hazard regression analysis, and the adjusted hazard ratio (95%CI) was 4.08 (1.20-14.19). In conclusion, we found that the XRCC1 194 (Arg>Trp) polymorphism was correlated with a better response to chemotherapy and a low risk of death in patients with gastric cancer.