We investigated the correlation between the response to chemotherapy in patients and excision repair cross-complimenta-ry group 1 gene (ERCC1) and xeroderma pigmentosum complemen-tation group F gene (XPF) polymorphisms and the effect of these polymorphisms on the clinical outcome of gastric cancer. Samples from a total of 255 patients with newly diagnosed and histopatho-logically confirmed primary gastric cancer were collected in our study. The ERCC1 rs11615, ERCC1 rs2298881, XPF rs2276465, and XPF rs6498486 polymorphisms were genotyped. Among the 255 patients, the median follow-up time was 29.7 months. A total of 103 patients (40.4%) died from gastric cancer during the follow-up period. We observed that the XPF rs6498486 CC genotype and the XPF rs2276465 GG genotype were associated with response to che-motherapy, with odds ratios and 95% confidence intervals of 3.88 (1.23-16.07) and 2.66 (1.17-6.45), respectively. In the Cox propor-tional hazards model, patients carrying the ERCC1 rs11615 AA gen-otype and the XPF rs2276465 GG genotype showed only a 0.22- and 0.30-fold increased risk of death from gastric cancer. We found that the XPF rs6498486 and XPF rs2276465 polymorphisms are mark-ers of response to oxaliplatin/5-fluorouracil-based chemotherapy in gastric cancer patients.