Aberrant Wnt/b-catenin signaling is a characteristic feature of colorectal cancer (CRC), therefore, understanding the underlying mechanisms of aberrant Wnt/b-catenin signaling will improve the treatment outcome of CRC. Expression of MNX1 in paired fresh CRC tissues and corresponding adjacent normal tissues were examined by qPCR and Western blotting. The levels of MNX1 in paraffin-embedded CRC specimens were detected by immunohistochemistry (IHC). The role of MNX1 in growth and proliferation of CRC cells was evaluated by MTT and colony formation assay. Luciferase reporter analysis and western blotting were carried out to explore the influence of MNX1 on Wnt/b-catenin signaling. The results showed that expression of MNX1 is markedly upregulated in CRC tissues and positively correlated with level of Ki67, and overexpression of MNX1 significantly promotes the proliferation of CRC cells. Further study showed that ectopic expression of MNX1 activates the Wnt/b-catenin signaling and upregulates the expression of c-Myc and CCND1, the downstream genes of Wnt/b-catenin signaling. Therefore, MNX1 plays an indispensable role in promoting of human CRC progression and may represent a novel therapeutic target for CRC.