The purpose of this articles is to determine whether the cytochrome P450 2E1 (CYP2E1) Rsa I/Pst I gene polymorphism is correlated with respiratory system cancers. Respiratory system cancers included lung cancer, laryngeal cancer, nasopharyngeal cancer, and cancers of other respiratory organs, which are the most common malignant tumors worldwide; the significant relationship between CYP2E1 Rsa I/Pst I gene polymorphism and some respiratory system cancer have been reported, but results of some other studies are controversial. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the association. PubMed, EMBASE, Cochrane Library Databases, China National Knowledge Infrastructure, and Wanfang Database (up to July 20, 2014) were searched for all case-control studies those mainly studied the relationship between CYP2E1 Rsa I/Pst I gene polymorphism and the susceptibility of respiratory system cancer. A total of 332 articles were collected, among which 34 studies that involved 7028 cases and 9822 controls fulfilled the inclusion criteria after being assessed by 2 reviewers. When stratified by cancer site, the C2/C2 polymorphism could increase the risk of nasopharyngeal cancer under the homozygote model (C2C2 vs C1C1: OR = 1.85, 95% CI = 1.20-2.85, P = 0.005) and recessive model (C2C2 vs C1C2/C1C1: OR = 1.89, 95% CI = 1.23-2.89, P = 0.003). Protection effect was found in lung cancer in heterozygote model (C1C2 vs C1C1: OR = 0.82, 95% CI = 0.74-0.91, P < 0.001), dominant model (C1C2/C2C2 vs C1C1: OR = 0.83, 95% CI = 0.76-0.90, P < 0.001), and allele contrast model (C2 vs C1: OR = 0.85, 95% CI = 0.73-1.00, P = 0.045). With regard to ethnicity subgroup analysis, there was significant association in Asian population in heterozygote model (C1C2 vs C1C1: OR = 0.85, 95% CI = 0.78-0.94, P = 0.001), dominant model (C1C2/C2C2 vs C1C1: OR = 0.88, 95% CI = 0.81-0.95, P = 0.001), and recessive model (C2C2 vs C1C2/C1C1: OR = 1.25, 95% CI = 1.01-1.53, P = 0.036). CYP2E1 Rsa I/Pst I gene polymorphism may reduce the risk of respiratory system cancer. Furthermore, significant association was also found in Asian populations.