Polymorphisms in XPG are considered to contribute to the clinical outcome of patients receiving platinumdrug chemotherapy. We aimed to investigate the role of five potential SNPs of XPG gene on the responseto platinum-based chemotherapy in advanced Chinese NSCLC patients. A total of 451 patients with newlydiagnosed and histopathologically confirmed primary NSCLC were consecutively collected. XPG rs2296147,rs4150261, rs17655, rs1047768 and rs2094258 were genotyped by the Taqman real-time polymerase chain reaction(PCR). In our study, we found patients carrying rs1057768 TT genotype had a significantly lower treatmentresponse when compared with the CC genotype (OR=0.38, 95% CI=0.18-0.78). Patients carrying rs1047768 TTgenotype showed a significantly short median PFS (11.2 months) and OS (13.6 months) than CC genotype, andthe hazard ratios (HR) for PFS and OS were 2.06 (1.01-4.50) and 2.29 (1.21-2.49), respectively. Moreover, wefound a significant decreased risk of death from NSCLC among patients carrying the rs2296147 TT genotypewhen compared with the CC genotype, the HR (95% CI) for OS being 0.50 (0.27-0.95). In conclusion, our studyfound that polymorphisms in rs1047768 C/T and rs2296147 C/T are associated with response to platinum-basedchemotherapy in advanced NSCLC, and XPG polymorphisms could be predictive of prognosis.