Esophageal squamous cell carcinoma (ESCC) has become one of the most common causes of cancer‑associated mortality worldwide. Transforming growth factor‑activated kinase (TAK1)‑binding protein 3 (TAB3) is essential for activation of the NF (NF)‑κB pathway in response to TAK1 activation. The NF‑κB pathway serves important roles in tumor cell proliferation and migration; however, the clinical relevance of TAB3 and its biological function in ESCC progression remain elusive. The present study investigated the expression and function of TAB3 in ESCC tissues, and its association with the clinical prognosis of patients. The results demonstrated that TAB3 expression was significantly increased in human ESCC cell lines and tissue samples, and the expression of TAB3 was associated with ESCC lymph node metastasis, T stage, pathological grade and Ki‑67 expression in 80 ESCC samples, as determined by immunohistochemistry. Patients with ESCC and high TAB3 expression exhibited worse overall survival. Furthermore, knockdown of TAB3 by small interfering RNA inhibited the proliferation of ESCC cells, and reduced the migration and invasion of ESCC cells. In addition, knockdown of TAB3 decreased the expression of the NF‑κB pathway in TE‑1 cells. Taken together, these results demonstrated that TAB3 may be a promising therapeutic target for the treatment of ESCC.