Wnt7α (wingless-type MMTV integration site family, member 7A) is a secreted glycoprotein that plays a critical role in tumorigenesis and development by controlling cell proliferation and differentiation. Whether Wnt7α has the properties of an oncogene or not is an interesting issue because of its diverse expression in different tumors. In the present study, Wnt7α protein expression was evaluated through immunohistochemistry and Western blot analysis. Univariate and multivariate analyses were applied to explore the associations between Wnt7α staining score and various clinical parameters, including overall survival (OS) and disease-free survival (DFS), and a total of 212 patients with colorectal cancer (CRC) were surveyed. Wnt7α was strongly expressed in most CRC tissues but weakly expressed in adjacent normal mucosa, colorectal adenomas, and colonic polyps. High levels of Wnt7α expression were strongly associated with tumor size (P = 0.006), lymph node involvement (P < 0.001), and the international tumor-node-metastasis (TNM) stage (P = 0.005). Patients with strong Wnt7α expression showed significantly poorer OS and DFS than patients with weak Wnt7α expression (P < 0.0001, both). Multivariate Cox analysis confirmed that Wnt7α protein expression and TNM stage are independent factors of adverse OS and DFS in CRC patients. Taken together, our results present evidence that Wnt7α overexpression is associated with an unfavorable prognosis and that positive Wnt7α, in addition to TNM stage, may be an independent prognosis factor influencing OS and DFS prediction in CRC patients.