To assess that the XRCC1 399Gln variant contributes to sensitivity to ionizing radiation treatment and is associated with progression-free and overall survival, one hundred and ninety-five lung cancer patients were recruited at the Asan Medical Center from 2000 to 2003. We determined the genotypes of the XRCC1 genes by PCR-RFLP. Kaplan-Meier survival curves and the log-rank test were used to analyze the effects of genotypes on survival. Hazard ratios, adjusted for age, sex, and other potential confounders, were calculated using the Cox-proportional hazard model. Patients carrying the 399Gln variant allele under radiotherapy only had a shorter progression-free and overall survival than those with the 399Arg homozygote. However, when we analyzed for the effect of the XRCC1 Arg399Gln polymorphism in the combined treatment of surgical resection and radiotherapy, we found that patients with the 399Gln variant allele had a longer progression-free and overall survival. This study shows different associations between the XRCC1 Arg399Gln polymorphism and progression-free or overall survival depending on treatment protocol in patients with NSCLC.