Methylenetetrahydrofolate reductase (MTHFR) has been demonstrated to be involved in carcinogenesis. Increasing individual studies have investigated the role of MTHFR C677T polymorphism in gastric cancer pathogenesis, but with inconsistent findings. The aim of this study was to clarify the potential association of the MTHFR C677T polymorphism with gastric cancer risk by pooling all available data from published case-control studies. We searched the PubMed, Embase, Web of Science, and Wanfang databases for all relevant publications to date. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95% CI) was calculated. Stratified analysis and sensitivity analysis were also carried out to estimate the strength of this association. A total of 25 case-control studies with 6,572 cases and 9,584 controls were retrieved. Overall, the ORs under five contrast models indicated that the MTHFR C677T variant was positively associated with gastric cancer risk (ORT vs. C = 1.21, 95% CI 1.10–1.34, P(OR) < 0.001; OR(TT vs. CC) = 1.47, 95% CI 1.22–1.76, P(OR) < 0.001; OR(TC vs. CC) = 1.20, 95% CI 1.03-1.40, P(OR) = 0.022; OR(TT + TC vs. CC) = 1.27, 95% CI 1.10-1.47, P(OR) = 0.001; OR(TT vs. CC + TC) = 1.29, 95% CI 1.15-1.46, P(OR) < 0.001). Stratified analyses according to ethnicity and source of controls further confirmed the significant correlations. The current meta-analysis provides strong evidence that the MTHFR C677T polymorphism may be a risk factor for gastric cancer among Asians and Caucasians.