BACKGROUND Genetic polymorphism in metabolic enzymes, which are involved in metabolism of environmental carcinogens, have been thought to be related to susceptibility of lung cancer. The aim of this study is to investigate the cytochrome P450 2D6(CYP2D6) genetic polymorphism distribution in Han population in Sichuan, China, and to evaluate the relationship between CYP2D6 genetic polymorphism and lung cancer susceptibility. METHODS PCR-RFLP was used to identify CYP2D6ch genotypes among 150 patients with primary lung cancer and 152 healthy controls, in Han population in Sichuan, China, and case-control study was used to analyze the relationship between genetic polymorphism and lung cancer susceptibility. RESULTS (1) The distribution frequency of CYP2D6ch C and T allele were 39.5% and 60.5% in control group and 46.3% and 53.7% in lung cancer group, respectively. There was no significant difference between the two groups (P=0.089). (2)The distribution frequency of C/C, C/T and T/T genotypes were 18.4%, 42.1% and 39.5% in control group, and 22.7%, 47.3% and 30.0% in lung cancer group, respectively. No significant difference was found between the two groups (P=0.215). (3) The individuals who carried with Non-T/T genotypes had a 2.084-fold increased risk with squamous cell carcinoma (95%CI 1.024-4.244, P=0.043) than those who carried with T/T genotype. (4) The lighter smokers ( < 30 pack-years) who carried with Non-T/T genotypes had a 2.92-fold increased risk with lung cancer (95%CI 1.087-7.828, P=0.033) than those who carried with T/T genotype. CONCLUSIONS CYP2D6ch Non-T/T genotypes are factors associated mail:zhouqh@mail.sc.cninfo.net) with increased risk of squamous cell carcinoma and also increase risk of lung cancer among lighter smokers.