Many epidemiological studies have evaluated the association between microRNA-499 rs3746444 A/G polymorphism and cancer risk, but published data are still inconclusive. Therefore, we performed a meta-analysis to evaluate the association between microRNA-499 rs3746444 A/G polymorphism and cancer susceptibility. The summary odds ratio (OR) with its 95% confidence interval (CI) was calculated to evaluate the association. Seventeen case-control studies with a total of 7,974 cancer cases and 9,404 controls were finally included into this meta-analysis. Overall, microRNA-499 rs3746444 A/G polymorphism was significantly associated with increased risk in both the domain model (GG/AG versus AA: OR = 1.17, 95% CI, 1.03-1.33, P = 0.02) and the heterozygote comparison model (AG versus AA: OR = 1.15, 95% CI, 1.01-1.32, P = 0.03) when all studies were pooled into the meta-analysis. Subgroup analysis by ethnicity showed that association between microRNA-499 rs3746444 A/G polymorphism and cancer susceptibility was significant in Asians, but not in Caucasians. In the subgroup analysis by cancer types, no risk of breast, liver, or lung cancers were found significantly associated with microRNA-499 rs3746444 A/G polymorphism in any of the genetic models. In summary, this meta-analysis suggests that microRNA-499 rs3746444 A/G polymorphism is associated with increased susceptibility to cancer in Asians. However, more well-designed studies with large sample size are needed to validate this association among different kinds of cancers.