This study aimed to investigate the effects of Ser/Cys polymorphism in hOGG1 gene, Arg/Pro polymorphismin p53 gene, smoking and their interactions on the development of lung cancer. Ser/Cys polymorphism inhOGG1 and Arg/Pro polymorphism in p53 among 124 patients with lung cancer and 128 normal people weredetected using PCR-RFLP. At the same time, smoking status was investigated between the two groups. Logisticregression was used to estimate the effects of Ser/Cys polymorphism and Arg/Pro polymorphisms, smoking andtheir interactions on the development of lung cancer. ORs (95% CI) of smoking, hOGG1 Cys/Cys and p53 Pro/Pro genotypes were 2.34 (1.41-3.88), 2.12 (1.03-4.39), and 2.12 (1.15-3.94), respectively. The interaction modelof smoking and Cys/Cys was super-multiplicative or multiplicative, and the OR (95% CI) for their interactionitem was 1.67 (0.36 -7.78). The interaction model of smoking and Pro/Pro was super-multiplicative with anOR (95%CI) of their interaction item of 5.03 (1.26-20.1). The interaction model of Pro/Pro and Cys/Cys wasmultiplicative and the OR (95%CI) of their interaction item was 0.99 (0.19-5.28). Smoking, hOGG1 Cys/Cys,p53 Pro/Pro and their interactions may be the important factors leading to the development of lung cancer.