Abstract: Objective To investigate the association between DNA double-strand break repair gene （DSBR）polymorphisms and prognosis of patients with non-small cell lung cancer(NSCLC). Methods PCR-RFLP and TaqMan probe technique were used to identify the polymorphism of 10 SNPs in DSBR gene, rs6869366, rs1056503, rs3734091, rs861539, rs861537, rs1799794, rs16942, rs144848, rs1805794 and rs2735383, in 679 NSCLC patients. Prognosis was analyzed by Kaplan-Meier, Log-rank test and Cox regression model. Results The estimated 5-year OS of NSCLC patients was 29.8%(95%CI：26.1%-33.5%). Subgroup analysis revealed that XRCC3rs861539 CT+TT was associated with lower death risk than CC in patients treated with chemotherapy（MST：32 vs. 60 months；HR=0.629，95%CI：0.411-0.962，P=0.032；aHR=0.623，95%CI:0.399-0.973，P=0.038）. BRCA1 rs16942 AG+GG was associated with worse survival than AA in patients with the squamous subtype（MST：24 vs. 31months；aHR=1.622，95%CI:1.139-2.310，P=0.007）. NBS1rs2735383GC+CC was associated with higher survival than GG in non-smoking female wtih adenocarcinoma（MST：41 vs. 32 months；aHR=0.420，95%CI:0.247-0.714，P=0.001）. XRCC3 rs861539CT+TT was associated with lower death risk than CC in clinic early-stage patients（aHR=0.444，95%CI:0.192-1.025，P=0.057）. NBS1rs1805794 CG+GG was associated with higher death risk than CC in clinic early-stage smoking men（aHR=2.768，95%CI:1.273-6.017，P=0.01）. XRCC3 rs861537AG or AA was associated with higher death risk than GG in clinic advanced patients（aHR=1.750，95%CI:1.021-3.001，P=0.042）. NSCLC patients with four or five unfavorable genotypes had a significantly worse OS than those with less than three unfavorable genotypes （aHR=1.153，95%CI:1.005-1.322, Ptrend=0.042）. Conclusion DSBR gene polymorphism may be a reference for the prognosis evaluation of NSCLC patients.