Although many epidemiologic studies investigated the methylenetetrahydrofolate reductase (MTHFR)polymorphisms and their associations with esophageal cancer, definite conclusions could not be drawn. To clarifythe effects of MTHFR polymorphisms on the risk of esophageal cancer, a meta-analysis was here performed inChinese populations. A total of 16 studies including 3,040 cases and 4,127 controls were involved in this metaanalysis.Overall, significant associations were found between the MTHFR C677T polymorphism and esophagealcancer risk when all studies in Chinese populations were pooled into the meta-analysis (T vs. C, OR = 1.19, 95%CI = 1.06–1.34; TT vs. CC, OR = 1.35, 95% CI = 1.07–1.70; TT+ CT vs. CC, OR = 1.29, 95% CI = 1.08–1.54;TT vs. CC + CT, OR = 1.19, 95% CI = 1.03–1.37). In subgroup analyses stratified by ethnicity and source ofcontrols, the same results were found in Kazakh (TT vs. CC, OR = 1.38, 95% CI = 1.02-1.87; TT + CT vs. CC,OR = 1.50, 95% CI = 1.03-2.18), in not stated populations (T vs. C, OR = 1.24, 95% CI = 1.08-1.42; TT vs. CC,OR = 1.47, 95% CI = 1.10-1.96; TT + CT vs. CC, OR = 1.30, 95% CI = 1.05-1.60; TT vs. CC + CT, OR = 1.32,95% CI = 1.12-1.56), and in hospital-based studies (T vs. C, OR = 1.34, 95% CI = 1.19-1.51; TT vs. CC, OR =1.81, 95% CI = 1.37-2.39; TT + CT vs. CC, OR = 1.51, 95% CI = 1.26-1.83; and TT vs. CC + CT, OR = 1.39,95% CI = 1.13-1.70). In conclusion, this meta-analysis provides evidence that the MTHFR C677T polymorphismcontributes to esophageal cancer development in Chinese populations.