Myeloperoxidase (MPO) is a phase I enzyme playing a crucial role in metabolically activating a wide range of procarcinogens, such as polycyclic aromatic hydrocarbons and aromatic amines. The G463A polymorphism in the promoter region of the MPO gene has been indicated in lung cancer risk. To investigate the precise association of MPO G463A polymorphism with the lung cancer risk, we performed this comprehensive meta-analysis with large available data published to date. The included 24 individual studies involving a total of 8,313 cases and 8,728 controls were identified by searching the PubMed, Embase, and Wanfang databases. The crude odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated to estimate the association. Stratified analyses by ethnicity, source of controls, smoking status, and histological types were also conducted. Overall, the MPO G463A polymorphism was negatively related to the development of lung cancer in the following genetic models (A vs. G, OR = 0.90, 95% CI = 0.82-0.99, P OR = 0.029; GA vs. GG, OR = 0.89, 95% CI = 0.80-0.98, P OR = 0.022; AA + GA vs. GG, OR = 0.89, 95% CI = 0.81-0.98, P OR = 0.023). Stratified analyses by ethnicity indicated that the variant genotype of MPO G463A was associated with a decreased risk of lung cancer in Asians and Caucasians. Similar findings were observed among the smokers and population-based case-control studies. The MPO G463A polymorphism seemed to exert no effect on lung adenocarcinoma and squamous cell carcinoma. The comprehensive meta-analysis shows that the polymorphism of MPO G463A is a protective factor for lung cancer, particularly among the populations of Asians, Caucasians, and smokers.