Objective: To investigate the effect of 2,3,5,4’-tetrahydroxy stilbene-2-Ο-β-D-glucoside (THSG) on TGFβ induced epithelial-mesenchymal transition (EMT) in HCT116 cells and further to explore the potential molecular mechanism. Methods: Transforming growth factor β (TGFβ) was used to induce EMT in HCT116 cells, the morphological changes were observed under inverted microscope, and EMT related molecular markers were detected by Western blot. Wound Healing assay, Transwell assay, inverted microscope were performed to detect whether THSG could reverse the motility, migration ability and morphological changes induced by TGFβ, the effect of THSG on EMT-related molecular markers and PI3K/AKT pathway were measured by Western blot. Results: TGFβ treated HCT116 cells transformed from round type to spindle-shaped form, compared with the losing of E-cadherin and increasing of vimentin, N-cadherin. However, combination treatment with THSG neutralized the effect of TGFβ on E-cadherin, vimentin, N-cadherin. Meanwhile, THSG treatment increase the expression of PTEN and suppress p-AKT expression. Moreover, THSG could inhibited TGFβ induced migration and motility ability (F=454.723, P<0.001; F=412.161, P<0.001). Conclusion: THSG can inhibit TGFβ induced EMT in colorectal cancer via PI3K/AKT pathway, and suppress the ability of motility and migration.