Abstract: Objective To detect the expressions of transforming growth factor-β (TGF-β)-activated kinase (TAK1) and TGF-β- activated protein kinase 1 (TAB1) in esophageal cancer tissues and explore their correlations with the clinicopathological features and prognosis of the patients. Methods The expressions of TAK1 and TAB1 in 84 esophageal cancer tissues and paired adjacent tissues was detected using immunohistochemical staining. The correlations of different patterns of TAK1 and TAB1 expressions (TAK1 alone, TAB1 alone, and both) with the clinicopathological features of the patients were analyzed. The correlation between TAK1 and TAB1 was assessed based on GEPIA datasets. Kaplan- Meier survival analysis was used to analyze the recurrence-free survival of the patients in relation with TAK1 and TAB1 expressions. Results TAK1 and TAB1 were highly expressed in 65.5% (55/84) and 52.4% (44/84) of the esophageal cancer tissues, respectively. The expression of TAK1, TAB1 and their co-expression were all correlated with tumor invasion depth, lymph node metastasis, and TNM staging (P< 0.05). A strong correlation was found between TAK1 and TAB1 expressions. A high expression of TAK1 and TAK1/TAB1 co-expression both predicted a poor recurrence-freed survival of the patients (P<0.05). Conclusion TAK1 and TAB1 are associated with the progression and prognosis of esophageal cancer and can serve as new prognostic biomarkers for esophageal cancer and as potential molecular targets for therapies.