Abstract: Objective To investigate the association of genetic variations (-1239G>C) in Cytochrome P450 2E1 gene with the prognosis of metastatic non-small cell lung cancer(NSCLC) patients. Methods We determined the genotypes of CYP2E1-1239G>C variants by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Statistical analysis was performed using the Sigma State 11.0 statistical software package. Kaplan-Meier Log-rank analysis and COX regression were used to conduct survival analysis. Results The median survival time of CYP2E1-1239GG genotype carriers was longer than that of carriers with -1239CC or CG genotypes carriers (55.7 vs. 24.2 months). The median survival time of the patients without distant metastasis was significantly longer than that with distant metastasis (59 vs. 23.1 months, P<0.001). We found that the metastatic NSCLC patients with at least one CYP2E1-1239C allele had shorter median survival time compared with those with -1239GG genotype (13 vs. 35.3 months, P=0.005). The Cox model analysis showed that CYP2E1 polymorphism was an independent factor for the prognosis of metastatic NSCLC patients(P<0.05). Conclusion The CYP2E1-1239G>C polymorphism is associated with the prognosis of metastatic NSCLC patients.