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Objective: Polymorphisms in XPG were considered to contribute to the clinical outcome of patients receiving platinum drug chemotherapy. We investigated the impact of several potential SNPs of XPG on the efficacy of platinum-based chemotherapy in NSCLC patients. Methodology: A total of 433 patients were consecutively selected between Nov. 2006 and Dec. 2007, and were followed-up up to Nov. 2011. The genotyping of six SNPs (rs2296147, rs751402, rs873601, rs4150375, rs17655 and rs2094258) were genotyped using the Taqman real-time PCR method with a 7900 HT sequence detector system. Results: Patients carrying CT+TT genotype of rs2296147 had a significantly longer median PFS (17.5 months) and OS (26.8 months) than CC genotype. Hazard ratio (HR) for PFS and OS in patients with CT+TT genotype of rs2296147 was respectively 0.73(0.51-0.97) and 0.66(0.48-0.99) when compare CC genotype, respectively. Similarly, patients with rs2094258 AG+GG genotype had a longer median progression time (18.4 months) and overall survival time (27.3 months) when compared with those with AA genotype, and HRs(95% CI) for PFS and OS were 0.44(0.34-0.78) and 0.51(0.39-0.82), respectively. Conclusions: Our study suggests rs2296147 CT+TT and rs2094258 AG+GG genotypes contribute to the better survival of NSCLC. Our study provides significant information on role of prognostic value of XPG SNPs, and detecting of XPG could be used as predictive markers toward individualizing NSCLC treatment strategies. [ABSTRACT FROM AUTHOR]