ObjectiveTo investigate effect of astragaloside Ⅳ on the proliferation， migration， and invasion of colorectal cancer HCT116 cells and the underlying molecular mechanism. MethodColorectal cancer HCT116 cells were classified into blank group （DMSO） and low-dose （15.7 mg·L^-1）， medium-dose （31.4 mg·L^-1）， and high-dose （62.8 mg·L^-1） astragaloside Ⅳ groups. After drug treatment， the morphological changes of HCT116 cells were observed under an inverted microscope. Cell viability was detected by cell counting kit-8 （CCK-8） assay， and the migration and invasion of cells were detected based on scratch assay and Transwell assay. The expression of cyclin-dependent kinase inhibitor （p21）， CyclinD₁， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the cells was examined by Western blot. ResultCompared with the blank group， cells in the three astragaloside Ⅳ groups demonstrated slow growth， low density， inconsistent morphology， nuclear shrinkage， degradation of cytoplasm， and high death rate. Moreover， cell viability decreased in a concentration-dependent manner in the astragaloside Ⅳ groups. Cell migration and invasion were inhibited （P<0.05， P<0.01）， and the inhibition rate was in positive correlation with the concentration of the astragaloside Ⅳ. The expression of pro-apoptotic protein Bax in low-dose， medium-dose and high-dose astragaloside Ⅳ groups increased gradually in a concentration-dependent manner， while the expression of p21， CyclinD₁ and anti-apoptotic protein Bcl-2 decreased gradually in a concentration-dependent manner compared with those in the blank group （P<0.05， P<0.01）. ConclusionAstragaloside Ⅳ can suppress the proliferation， migration， and invasion of colorectal cancer HCT116 cells and promote the apoptosis， thus inhibiting the occurrence and development of colorectal cancer.