AIM: To evaluate the potential association of xeroderma pigmentosum group D (XPD) codon 751 variant with outcome after chemo-radiotherapy in patients with resected gastric cancer. METHODS: We used PCR-RFLP to evaluate the genetic XPD Lys751Gln polymorphisms in 44 patients with stage III (48%) and IV (20%) gastric cancer treated with surgery following radiation therapy plus 5-fluorouracil/ leucovorin based chemotherapy. RESULTS: Statistical analysis showed that 75% (12 of 16) of relapse patients showed Lys /Lys genotype more frequently (P = 0.042). The Lys polymorphism was an independent predictor of high-risk relapse-free survival from Cox analysis (HR: 3.07, 95% CI: 1.07-8.78, P = 0.036) and Kaplan-Meir test (P = 0.027, log-rank test). CONCLUSION: XPD Lys751Gln polymorphism may be an important marker in the prediction of clinical outcome to chemo-radiotherapy in resected gastric cancer patients.