Abstract: Objective To evaluate the effect of high glucose on the proliferation of colon cancer cells, and investigate the mechanism of the effect of Wnt inhibitory factor 1 （WIF1） on the proliferation of colon cancer cells under high glucose state through the Wnt/β-catenin signaling pathway. Methods Colon cancer cell line SW620 cells were treated with different doses of D-glucose. The expressions of proliferation-associated mRNA and protein were measured by real-time fluorescent quantitative PCR （qPCR） and Western blot. The proliferation ability of SW620 cells was measured by cell proliferation assay, cell counting assay and colony formation assay. The expression levels of WIF1 and β-catenin were detected by qPCR and Western blot. After regulating the expression of WIF1 by the transfection with siRNA and over-expressed plasmid, the effect of WIF1 upon the proliferation ability and the expression of β-catenin in SW620 cells was evaluated. Results Along with the increase in glucose concentration, the proliferation ability of SW620 cells was significantly increased, the expression of WIF1 was remarkably down-regulated and the expression of β-catenin was significantly up-regulated （all P < 0.05）. The proliferation ability of SW620 cells was considerably increased and the expression of β-catenin was significantly up-regulated after down-regulating the WIF1 expression （all P < 0.05）. However, after the over-expression of WIF1, cell proliferation ability was significantly inhibited and the expression of β-catenin was remarkably down-regulated （all P < 0.05）. Conclusion Down-regulation of WIF1 expression under high glucose state may promote the proliferation of colon cancer cells under high glucose state via the activation of Wnt/β-catenin signaling pathway.