Abstract: ObjectiveTo explore the relationship between the polymorphisms of phase Ⅱ metabolic gene NQO1 codon 187 and the susceptibility to lung cancer and to evaluate possible interaction between NQO1 and sm oking with the risk of lung cance.MethodsA case-control study including 396 new diagnosed lung cancer cases and 465 healthy resident controls was conducted The PCR-based restriction fragment lengthpolymorphism (RLFP) techniquewas applied to analyze the NQO1 polym orphism at Pro187 Ser loci.The data were analyzed with logistic regression model.ResultsThe frequency of allele Pro and Ser in case group was 50.88% and 49.12%,respectively; while in the control group, it was 56.13% and 43.87%.A statistical significant difference was observed(P=0.0296).The carriers of Ser/Ser had higher risk of lung cancer than Pro/Pro carriers(adjusted odds ratio AOR=1.53, 95% confidence interval95% CI=1.O1-2.32).Moreover, the carriers of Ser/Ser had a much higher risk of adenocareinom a than Pro/Pro carriers (AOR=2.16, 95% CI=1.16-4.02).The smokers who carried mutative genotype of Ser/Ser possessed a 1.5 tines higher risk of lung cancer than the smokers who carried at least one wfill allele Pra.Furthermore, significant synergistic effect was seen between smoking and mutative genotype of NQO1 (Ser/Ser) in the occurrence of adenocarcinom a (AOR=2.74, 95% CI=1.00-7.49).Conclusion.The results suggested that genetic polym orphism of phase Ⅱ metabolic gene NQO1 colon 187 might play an inpor tant role in the development of lung cancer.Furthermore, smoking might hold synergistic effect with the polym orphisms of NOO1 colon 187 in the occurrence of lune cancer.