Numerous studies have investigated the risk of colorectal cancer (CRC) associated with the polymorphism of DNA methyltransferase 3B (DNMT3B) 149 C>T, but results have been inconsistent. We performed this meta-analysis to drive a more precise estimation of the association between this polymorphism and risk of CRC. A comprehensive search was conducted to identify all case-control studies of the -149C>T polymorphism of DNMT3B and CRC risk. A total of seven eligible studies, including 2,666 cases and 4,022 controls, relating the DNMT3B polymorphism of -149C>T to the risk of CRC were identified. It suggested no significant associations between -149C>T polymorphism of DNMT3B gene and the risk of developing CRC in the recessive, dominant, and co-dominant models (for CC versus TT: OR = 0.90, 95% CI = 0.90-1.25, P heterogeneity = 0.37; for recessive model: OR = 0.54, 95% CI = 0.28-1.04, P heterogeneity = 0.00001; for dominant model: OR = 1.07, 95% CI = 0.93-1.23, P heterogeneity = 0.83; and for C allele versus T allele: OR = 0.70, 95% CI = 0.43-1.13, P heterogeneity = 0.00001). In the subgroup analysis, there is no significant associations were also found in European populations (for CC versus TT: OR = 1.09, 95% CI = 0.92-1.30, P heterogeneity = 0.88; for recessive model: OR = 1.00, 95% CI = 0.88-1.13, P heterogeneity = 0.14; for dominant model: OR = 1.50, 95% CI = 0.89-2.54, P heterogeneity = 0.00001; and for C allele versus T allele: OR = 0.70, 95% CI = 0.38-1.28, P heterogeneity = 0.00001). In conclusion, no significant association was found between the -149C>T polymorphisms in DNMT3B and CRC susceptibility.