Objective：To investigate the effect of B cell lymphoma 6 member B（BCL6B） on the proliferation and migration of human colorectal cancer cell line HCT116，and to explore its possible mechanism. Methods：Quantitative polymerase chain reaction（qPCR） and Western blot were used to detect and compare the endogenous expression of BCL6B in FHC and HCT116 cells. Liposome method was used to transfer the pcDNA3.1-BCL6B to HCT116 and the control group with empty vector was set. MTT assay，flow cytometry，wound healing assay and transwell chamber assay were used to detect the influence on proliferation，cycle and migration ability of cancer cell. Western blot was adopted to detect the expression of β-catenin，p-GSK3β，CyclinD1，MMP-7 and E-cadherin. Results：According to qPCR and Western blot，BCL6B expression was notably repressed in HCT116 cells as compared with FHC cells（P=0.017），and expression of BCL6B was significantly increased in HCT116 cells after transfection with pcDNA3.1-BCL6B for 48 h（P=0.000）. Compared with those in the control group，the OD492 value of HCT116 cells at the 4d time-point was decreased by 41.79% （P=0.040），and the percentage of cells in G1 phase was increased by 62.09%（P=0.001），48 h wound healing rate and transmembrane cells of HCT116 cells in the BCL6B group were significantly reduced（P=0.001）. The protein levels of β-catenin，p-GSK3β，CyclinD1 and MMP-7 of HCT116 cells in the BCL6B group were dropped by 65.66%（P=0.028），62.03%（P=0.001），60.87%（P=0.021） and 50.88%（P=0.030），respectively. E-cadherin was increased by 63.64%（P=0.018）. Conclusion：BCL6B inhibits the proliferation and migration of HCT116 cells，and its mechanism may involve in the inhibition of Wnt/β-catenin pathway.