Background: To study the relationship of susceptibility to lung cancer with the gene polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1, GSTP1 and smoking status in Han and Mongolian populations of Inner Mongolia, an autonomous region of China. Materials and Methods: PCR-RFLP, allele-specific and multiplex PCR were employed to identify the genotypes of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 in a case-control study of 322 lung cancer patients diagnosed by bronchoscopy and 456 controls free of malignancy. Results: There is a significant difference in genotypic frequency of GSTT1 of healthy Mongolian and Han subjects. A statistically prominent association was found between CYP1A1 Msp1 (vt/vt) (OR=4.055, 95%CI:2.107-7.578, p=0.000), GSTM1 (-) (OR=2.290, 95%CI:1.467-3.573, p=0.000) and lung cancer in Mongolians. Similarly, in the Han population, CYP1A1 Msp1 (vt/vt) (OR=3.194, 95%CI:1.893-5.390, p=0.000) and GSTM1 (-) (OR=1.884, 95%CI:1.284-2.762, p=0.001) carriers also had an elevated risk of lung cancer. The smokers were more susceptible to lung cancer 2.144 fold and 1.631 fold than non-smokers in Mongolian and Han populations, respectively. The smokers who carried with CYP1A1 Msp1 (wt/vt+vt/vt), exon7 (Val/Val+Ile /Val), GSTM1 (-), GSTM3 (AB+BB), and GSTT1 (-) respectively were found all to have a high risk of lung cancer. Conclusions: CYP1A1 Msp1 (vt/vt) and GSTM1 (-) are risk factors of lung cancer in Han and Mongolian population in the Inner Mongolia region. The smokers with CYP1A1 Msp1 (wt/vt+vt/vt), CYP1A1 exon7 (Val/Val+Ile /Val), GSTM1 (-), GSTM3 (AB+BB), and GSTT1 (-) genotypes, respectively, are at elevated risk of lung cancer.