Objective To investigate the correlation between the distribution of G681A and G636A polymorphisms in CYP2C19 gene and the risk of lung cancer. Methods The peripheral blood DNA was extracted from 293 patients with lung cancer and 300 healthy controls. The genotyping was conducted by using the real-time fluorescent polymerase chain reaction. Both the genotype and allele distributions were compared in patients with lung cancer and healthy controls. Results The CYP2C19*2/*3 genotype in the lung cancer group was significantly higher than those in the controls （18.77% vs 5.67%；P=0.000）. The CYP2C19*1/*2 genotype in the healthy control was significantly higher than those in lung cancer group (30.67% vs 13.99%；P＝0.000). The frequencies of weak metabolic gene of CYP2C19 were more than one times in the controls （33.45% vs 15.33%）. Multivariate logistic regression analysis showed that the poor metabolizer gene of CYP2C19 may be an independent risk factor for lung cancer (P=0.000，OR:2.755, 95%CI: 1.748～4.343). Conclusion The poor metabolizer gene of CYP2C19 might be related to the occurrence of lung cancer.