Overexpression of MDM2 may attenuate the P53 stress response pathway through direct blocking of P53 transcriptional activity and mediating P53 degradation. Two promoter polymorphisms (one is a T to G substitution at the intronic P53-response promoter, and the other is a 40-bp insertion/deletion polymorphism in the constitutive promoter) were identified, and recently the T/G substitution (SNP309) has been demonstrated to alter the levels of MDM2 gene products. In this molecular epidemiological study with 717 incident lung cancer cases and 1,083 cancer-free controls, we genotyped these 2 promoter polymorphisms of MDM2 and evaluated their associations with risk of lung cancer. We found that there were no significant associations between MDM2 SNP309 variant genotypes and lung cancer risk (adjusted OR = 1.20, 95% CI = 0.95-1.53 for TG and adjusted OR = 1.12, 95% CI = 0.85-1.48 for GG, respectively). Similarly, we did not find evidence for any association between risk of lung cancer and MDM2 insertion/deletion polymorphism. The findings suggest that these two MDM2 promoter polymorphisms may not play a major role in lung cancer susceptibility in this Chinese population.