The rapidly increasing of cancer risk nationwide and worldwide has threatened human health and caused the changes of disease and death spectrum. MicroRNA (MiRNA) as cancer biomarker on susceptibility has enjoyed a high level of concern. This article will discuss the association between miR-146 rs2910164 polymorphism and cancer susceptibility in 38 independent case-control studies from 34905 individuals. The 38 case-control studies which were searched from PubMed were used for conducting a meta-analysis. There were 14670 cases and 20235 controls. ORs and 95% CIs were used for reflecting the strength of association between miR-146a rs2910164 polymorphism and cancer susceptibility. Subgroup analysis based on the cancer type, ethnicity and study designs. All analysis were performed by using the Stata 11.0 software. MiR-146a rs2910164 polymorphism and overall cancer susceptibility were significantly uncorrelated in all genetic models. In the subgroup analysis for cancer types, miR-146a rs2910164 polymorphism was associated with the susceptibility of lung cancer (CC vs. GG: OR 1.275, 95% CI 1.117-1.455 (P = 0.000); CC + CG vs. GG: OR 1.166, 95% CI 1.052-1.293 (P = 0.003); CC vs. CG + GG: OR 1.239, 95% CI 1.116-1.375 (P = 0.000); C vs. G OR 1.151, 95% CI 1.080-1.227 (P = 0.000)) and nasopharyngeal carcinoma (CC vs. GG: OR 1.713, 95% CI 1.183-2.479 (P = 0.004); CC vs. CG + GG: OR 1.672, 95% CI 1.330-2.103 (P = 0.000); C vs. G: OR 1.400, 95% CI 1.181-1.659 (P = 0.000)), but it was not associated with hepatocellular carcinoma and gastric cancer. However, in the other subgroup analysis by ethnicity and study designs, no significant associations were found. MiR-146a rs2910164 polymorphism might be associated with the susceptibility to lung cancer and nasopharyngeal carcinoma.