Activin is a multifunctional growth and differentiation factor of the growth factor-beta (TGF-β) superfamily,which inhibits the proliferation of colon cancer cells. It induces phosphorylation of intracellular signalingmolecules (Smads) by interacting with its type I and type II receptors. Previous studies showed that humanactivin receptor-interacting protein 2 (hARIP2) can reduce activin signaling by interacting with activin typeII receptors; however, the activity of hARIP2 in colon cancer has yet to be detailed. In vitro, overexpression ofhARIP2 reduced activin-induced transcriptional activity and enhanced cell proliferation and colony formationin human colon cancer HCT8 cells and SW620 cells. Also, hARIP2 promoted colon cancer cell apoptosis,suggesting that a vital role in the initial stage of colon carcinogenesis. In vivo, immunohistochemistry revealedthat hARIP2 was expressed more frequently and much more intensely in malignant colon tissues than in controls.These results indicate that hARIP2 is involved in human colon tumorigenesis and could be a predictive makerfor colon carcinoma aggressiveness.