Background: The MTHFR C677T polymorphism is a genetic alteration affecting an enzyme involved in folate metabolism, but its relationship to host susceptibility to prostate cancer remains uncertain. The aim of this study was to investigate the association between MTHFR C677T polymorphism and prostate cancer by performing a meta-analysis. Materials and Methods: Pubmed and Web of Science databases were searched for case-control studies investigating the association between MTHFR C677T polymorphism and prostate cancer. Odds ratios (OR) and 95% confidence intervals (95%CI) were used to assess any link. Results: A total of 22 independent studies were identified, including 10,832 cases and 11,993 controls. Meta-analysis showed that there was no obvious association between MTHFR C677T polymorphism and risk of prostate cancer under all five genetic models. There was also no obvious association between MTHFR C677T polymorphism and risk of prostate cancer in the subgroup analyses of Caucasians. In contrast, MTHFR C677T polymorphism was associated with increased risk for prostate cancer in Asians with the allele model (C vs G: OR=1.299, 95 %CI =1.121-1.506, P=0.001, P heterogeneity =0.120, I 2 =45%), additive genetic model (CC vs TT: OR =1.925, 95 % CI= 1.340-2.265, P=0.00, P heterogeneity =0.587, I 2 =0.00%), recessive model (CC vs TT+TC: OR= 1.708, 95 % CI= 1.233-2.367, P=0.001, P heterogeneity =0.716, I 2 =0.00%), and heterozygote genetic model (CT vs TT: OR=2.193, 95 % CI =1.510-3.186, P=0.000, P heterogeneity =0.462, I 2 =0.00%). Conclusions: These results suggest that the MTHFR C677T polymorphism does not contribute to the risk of prostate cancer from currently available evidence in populations overall and Caucasians. However, the meta analysis indicates that it may play a role in prostate cancer development in Asians.