Objective：To evaluate the relation between the single nucleotide polymorphism of CYP2D6 gene G4268C and the genetic susceptibility to lung cancer. Methods： A case-control study was conducted among 118 lung cancer patients and 118 control subjects （matched for sex, age） to investigate the role of CYP2D6 gene G4268C polymorphism in lung cancer; PCRRFLP was used to identify the genotypes of polymorphism. Logistic regression was used to analyze the relationship between polymorphism and genetic susceptibility to lung cancer. Results： The frequency of G4268→C mutation in case and control group were 69.49% and 75.00%, respectively. Non-C4268/C genotype （including G4268/G and G4268/C genotype） was correlated to the high risk of lung cancer, with OR adjusted by gender, age and smoking being 1.80 （9% CI= 1.06-3.06）, especially to lung adenocarcinoma （OR being 2.95[95% CI= 1.39-6. 233）. After stratified analysis of smoking history and adjusting by gender and age, it was revealed that non-C4268/C genotype was associated with significantly increased risk of lung cancer in non-smokers and light-smokers group, with OR=2. 12 （95% CI=1. 03-4. 36） and OR= 3. 75 （950/00 CI=1. 15-12. 22）, respectively. Conclusion： C4268/C genotype may be a protective factor in lung adenocarcinoma patients and may decrease the risk of lung cancer in non-smokers and light-smorkers.