Objective: To investigate the expression of transforming growth factor β-activated kinase 1 (TAK1) in colon cancer and the clinical significance. Methods: Surgical specimens from 141 patients with colon cancer were collected. The TAK1 expression in colon cancer tissues and their adjacent normal tissues were determined by immunohistochemical staining, and the relations of TAK1 expression with clinicopathologic factors as well as prognosis of the patients were analyzed. Meanwhile, the K-ras gene mutation in the colon cancer tissues was detected, and the relationship between TAK1 expression and K-ras gene mutation was examined. Results: The positive expression rate of TAK1 in colon cancer tissues was significantly higher than that in adjacent normal tissues (68.8% vs. 16.3%, P<0.05). The positive TAK1 expression was significantly associated with Dukes stage, degree of tumor differentiation and lymph node metastasis (P<0.05), and the 5-year survival rate in patients with TAK1 positive tumor was significantly lower than in those with its low expression(P<0.05). The incidence of K-ras gene mutation in TAK1 positive colon cancer tissues was significantly higher than that in those with TAK1 negative expression (52.6% vs. 13.6%, P<0.05). Conclusion: TAK1 may be involved in malignant progression of colon cancer, and its expression is probably related to K-ras gene mutation.