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Objective: To explore the relationship between cytochrome P450 2E1 (CYP2E1) RsaⅠ/PstⅠ and Dral polymorphism and lung cancer susceptibility in Mongolian and Han population in Inner Mongolia of China. Methods: CYP2E1 RsaⅠ/PstⅠ and DraⅠ polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 64 lung cancer patients, 150 healthy Mongolian and 150 healthy Han individuals.The distribution of genotype and allele frequencies of CYP2E1 RsaⅠ/PstⅠ and DraⅠ polymorphisms were studied. Results: The risk of lung cancer was increased in individuals with CYP2E1 (cl/cl) and CYP2E1 (DD) with OR values of 2.431 (95％Cl=1.082-5.460) and 2.778 (95％Cl=1.358-5.683) respectively (P＜0.05). When CYP2E1 RsaⅠ/PstⅠ and DraⅠ polymorphisms were combined, the risk of lung cancer was reduced in individuals with CYP2E1 (cl/c2+c2/c2 and DD+CC) with OR values of 0.233 (95％Cl=0.088-0.615, P＜0.05). In smokers, the susceptibility to lung cancer was higher in the individuals with CYP2E1 (c1/c1) and CYP2E1 (DD) than in the individuals with c2 and C allele (P＜0.05, OR =2.643 and 4.308 respectively). There was no significant difference in distribution of CYP2E1 genotype frequency between healthy Mongolian, Han population and lung cancer patients, healthy controls in Inner Mongolia. Conclusion: CYP2E1 (c1/c1) and CYP2E1 (DD) are predisposing factors of lung cancer in population in Inner Mongolia. CYP2E1 (c2 + C) co-mutation may decrease the risk of lung cancer. Smoking exerts synergetic effect with CYP2E1 (c1/c1) and CYP2E1 (DD) on the occurrence of lung cancer.