The Wnt signaling is an important pathway in the process of development and oncogenesis. Over 90% of colon cancer patients have genetic alteration in Wnt genes such as β-catenin, APC resulting in activation of Wnt signal. While the canonical Wnt signaling has focused on β-catenin-mediated transcriptional regulation, recent studies suggested that Wnt pathway also plays an important role in EMT. The epithelial-mesenchymal transition (EMT) is implicated in tumorigenesis and cancer progression, and canonical Wnt signaling tightly controls Snail, a key transcriptional repressor of EMT. While the suppression of canonical Wnt signaling molecules reverting Wnt and EMT have not been yet. Meanwhile, the antihelminthic niclosamide has been identified as a potent inhibitor of many oncogenic signaling pathways although its molecular targets have not yet been clearly identified. In this study, we showed that niclosamide directly targets Axin-GSK3 interaction, at least in part, resulting in suppression of Wnt/Snail-mediated EMT. In vitro and in vivo, disruption of Axin-GSK3 complex by niclosamide induced mesenchymal to epithelial reversion at nM concentrations, accompanied with suppression of the tumorigenic potential of colon cancer. Niclosamide treatment successfully attenuated Snail abundance while increasing E-cadherin abundance in xenograft tumor. Notably, oral administration of niclosamide significantly suppressed adenoma formation in an APC-Min (multiple intestinal neoplasia, APC△850) mice model, indicating that niclosamide is an effective therapeutic for familial adenomatosis polyposis (FAP) patients. In this study, we identified small molecule inhibitor for Axin-GSK3 interaction, resulting in attenuation of Wnt pathwy as well as reversion of EMT in colorectal cancer cells. In turn, Axin-GSK3 interaction is the novel therapeutic target of colon cancer, and revealed a repositioned therapeutics for FAP patients.