Objective: Excision repair cross-complimentary group 2 (ERCC2) is one of the important DNA repair genes.ERCC2 codon 751 polymorphism has been shown to modulate cancer risk. We therefore assessed the relationship between the ERCC2 polymorphism and the susceptibility to lung cancer in nonsmoking females via a hospital-based case-control study. Methods: There were 105 lung cancer cases and matched healthy controls in this study. Information concerning demographic and risk factors was obtained, each person donated 2 ml blood for biomarker testing. ERCC2 genotypes were determined by PCR-RFLP method. All of the statistical analyses were performed with SPSS (v 12.0). Results: All of the subjects in this study were nonsmoking females in Shenyang.There was significant difference between the frequencies of ERCC2 polymorphism in cancer cases and controls (P＜0.05). The frequencies of ERCC2 751 Gin allele were 6.2% in controls and 13.8% in cancer cases. The individuals with Lys/Gln+Gln/Gln combined genotype were at an increased risk for lung cancer as compared with those carrying the Lys/Lys genotype (adjusted OR=2.80, 95%=CI 1.21-6.48). We analyzed the environmental risk factors for lung cancer in nonsmoking females. The cancer patients showed a higher prevalence of exposure to cooking fumes compared with controls (OR=2.44, P＜0.05). Furthermore, an interaction between exposure to cooking fumes and the variant ERCC2 751 Gln allele on the risk of lung cancer was observed. Individuals with both risk genotype and exposure to cooking fumes had a higher risk of cancer than those with only one of them.Conclusion: The above findings indicate that the genetic polymorphism in the ERCC2 codon 751 is associated with the risk of lung cancer in nonsmoking females.