Objective To investigate the polymorphisms of CYP1A1 and GSTM1 genes as well as their separate and combined effects on individual susceptibility to lung cancer. Methods This study was conducted in Jiangsu Province. In the matched 106 pairs of patients with lung cancer and non-cancer control persons,genomic DNA were prepared from peripheral blood samples. The genotypes of CYP1A1 Ile/Val and GSTM1+/0 polymorphisms were detected by the allele-specific (AS)-PCR and multi-differential(MD)-PCR. Results Individuals with genotype Val/Val of CYP1A1,genotype 0/0 of GSTM1, combined genotypes GSTM1 0/0 and CYP1A1 Val/Val, or combined genotypes GSM1 0/0 and CYP1A1 Ile/Val had higher relative risk than those with the corresponding common genotypes and combined genotypes; their odds ratios were 4.02(P=0.03), 1.92(P=0.019), 9.38(P=0.04) and 3.27(P=0.01), respectively. Conclusion There is a synergy of susceptible genotypes GSTM1 0/0 and CYP1A1 Val/Val or CYP1A1 Ile/Val to enhance the individual susceptibility to lung cancer.