We focused on OGG1 Ser326Cys, MUTYH Gln324His, APEX1 Asp148Glu, XRCC1 Arg399Gln, and XRCC3 Thr241Met and examined the relationship between the different genotypes and survival of Japanese lung cancer patients. A total of 99 Japanese lung cancer patients were recruited into our study. Clinical data were collected, and genotypes of the target genes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Survival analysis to verify the impact of these gene polymorphisms on the clinical outcome of lung cancer showed that lung squamous cell carcinoma patients with the Thr/Met genotype at XRCC3 had a significantly shorter survival time than those with the Thr/Thr genotype (13 months versus 48 months; log-rank test, p < 0.0001). Cox regression analysis showed that the carriers of XRCC3 genotypes were at a significantly higher risk [adjusted hazard ratio (HR) = 9.35, 95% confidence interval (CI) = 2.52-34.68, p = 0.001; adjusted HR = 9.05, 95% CI = 1.89-44.39, p = 0.006]. Our results suggest that XRCC3 Thr241Met may act as a favorable prognostic indicator for lung squamous cell carcinoma patients.