There is a possible association between myeloperoxidase (MPO) 463G>A polymorphism and risk of lung cancer, but previous studies report conflicting results. We performed a meta-analysis of available molecular epidemiologic studies to comprehensively assess the association between MPO 463G>A polymorphism and risk of lung cancer. A systemic literature search was performed in Pubmed, Embase, and Wanfang databases for molecular epidemiologic studies on the association MPO 463G>A polymorphism and risk of lung cancer on March 16, 2013. The pooled odds ratios (ORs) with their 95% confidence interval (95% CI) were calculated to assess the strength of the association. Twenty-six individual case-control studies with a total of 18,433 subjects (7,752 cases and 10,681 controls) were finally included into the meta-analysis. Overall, MPO 463G>A polymorphism was significantly associated with decreased risk of lung cancer under two main genetic comparison models (for A versus G, OR = 0.91, 95 % CI 0.83-0.99, P = 0.035; for AG/AA versus GG, OR = 0.90, 95% CI 0.81-0.99, P = 0.029). Meta-analysis of studies with high quality also showed that MPO 463G>A polymorphism was significantly associated with decreased risk of lung cancer under two main genetic comparison models (for A versus G, OR = 0.91, 95% CI 0.83-0.99, P = 0.035; for AG/AA versus GG, OR = 0.90, 95% CI 0.80-0.99, P = 0.048). Subgroup analysis by ethnicity further showed that there was a significant association between MPO 463G>A polymorphism and decreased risk of lung cancer in Caucasians but not in Asians. The meta-analysis suggests that MPO 463G>A polymorphism is associated with decreased risk of lung cancer, especially in Caucasians.