Abstract: Objective To evaluate the relationship between methionine synthase reductase(MTRR) A66G genetic polymorphism and the risk of pediatric acute lymphoblastic leukemia(ALL). Methods Relevant literatures were extensively searched in PubMed, Elsevier, Embase, China National Knowledge Infrastructure and Wanfang Databases for collecting the case-control studies investigating the relationship between MTRR A66G genetic polymorphism and pediatric ALL. Odds ratios(ORs) with 95% confidence intervals(CIs) were applied to assess the strength of association. The RevMan 5.2 software was applied for heterogeneity test and combined ORs and their 95%CIs calculation. Publication bias was assessed through funnel plot and sensitivity analysis was performed by sequential remove individual studies to assess the stability of the results. Results Seven studies bearing 2,326 cases and 3,090 controls met the inclusion criteria and were included in the Meta-analysis. There was no significant heterogeneity among the included studies and fixed-effects model was applied to combine the data. The results suggested that there was significant association between MTRR A66G polymorphism and pediatric ALL risk in overall comparisons under homozygote and dominant genetic models(GG vs. AA: OR=0.81, 95%CI: 0.69-0.95, P=0.009; AG+GG vs. AA: OR=0.87, 95%CI: 0.77-0.98, P=0.03). In the subgroup analysis by ethnicity, significant association was found in Caucasians (AG vs. AA: OR=0.84, 95%CI: 0.72-0.99, P=0.04; GG vs. AA: OR=0.79, 95%CI: 0.66-0.95, P=0.01; AG+GG vs. AA: OR=0.82, 95%CI: 0.71-0.96, P=0.01). No significant publication bias was detected by funnel plot and sensitivity analysis suggested the robustness of the results. Conclusion The present Meta-analysis suggests that MTRR A66G polymorphism is associated with pediatric ALL risk, especially in Caucasian populations.