The aim of this study was to examine the association between the -149C>T polymorphism of DNA methyltransferase 3B (DNMT3B) and colorectal cancer (CRC) susceptibility. A comprehensive search was conducted to identify all case-control studies of the -149C>T polymorphism of DNMT3B and CRC risk. Statistical analysis was performed with the software program Stata (version 12.0) and Review Manager (version 5.0). A total of seven eligible studies, including 2,666 cases and 4,022 controls, associating the DNMT3B polymorphism of -149C>T with the risk of CRC were identified. These studies suggested no significant associations between the -149C>T polymorphism of the DNMT3B gene and the risk of developing CRC in the recessive, dominant and co-dominant models [for CC vs. TT: odds ratio (OR), 0.90; 95% confidence interval (CI), 0.90-1.25; P=0.37; for the recessive model: OR, 0.54, 95% CI, 0.28-1.04; P<0.00001; for the dominant model: OR, 1.07; 95% CI, 0.93-1.23; P=0.83 and C allele vs. T allele: OR, 0.70; 95% CI, 0.43-1.13; P<0.00001]. In the subgroup analysis, no significant associations were found in the European populations (for CC vs. TT: OR, 1.09; 95% CI, 0.92-1.30; P=0.88; for the recessive model: OR, 1.00; 95% CI, 0.88-1.13; P=0.14; for the dominant model: OR, 1.50; 95% CI, 0.89-2.54; P<0.00001 and C allele vs. T allele: OR, 0.70; 95% CI, 0.38-1.28; P<0.00001). No significant association was found between the -149C>T polymorphism in DNMT3B and CRC susceptibility.