We conducted a cohort study to investigate whether 3 potential single nucleotide polymorphisms (SNPs) in the xeroderma pigmentosum complementation group G (XPG) gene could predict the survival of advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based doublet chemotherapy. We enrolled 262 patients with histologically confirmed NSCLC between November 2007 and December 2008 in this study. The 3 SNPs (rs2296147T>C, rs2094258C>T, and rs873601G>A) were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Older age, Eastern Cooperative Oncology Group performance score ≥2 and higher disease stage were associated with shorter survival. In the Cox proportional hazard model, patients carrying the rs2296147 TT genotype and the T allele had a significantly reduced risk of developing progressive disease or dying from NSCLC. The HRs (95%CI) were 0.31 (0.13-0.73) and 0.44 (0.24-0.83) for progression-free survival and 0.32 (0.14-0.71) and 0.54 (0.32-0.98) for overall survival, respectively. Moreover, advanced NSCLC patients carrying the rs2094258 GG and the G allele had a significantly decreased risk of developing progressive disease. The HRs (95%CI) for the rs2094258 GG genotype and the G allele were 0.35 (0.16-0.80) and 0.45 (0.23-0.86) for overall survival, respectively. We suggest that the rs2296147 and rs2094258 polymorphisms could be used as surrogate markers, leading to individualization of NSCLC treatment strategies.