Zinc finger E-box binding homeobox factor 1 (ZEB1), as a crucial mediator of "epithelial-mesenchymal transition," contributes to malignant progression of various epithelial tumors. However, its involvement in human esophageal squamous cell carcinoma (ESCC) remains unclear. In order to investigate the expression pattern of ZEB1 in ESCC tissues and evaluate its associations with tumor progression and patients' prognosis, 100 pairs of formalin-fixed and paraffin-embedded cancerous and adjacent noncancerous tissues from patients with ESCC were used to detect the expression pattern of ZEB1 by immunohistochemistry. Then, the association between ZEB1 expression, clinicopathological parameters, and prognosis of ESCC was examined. We also performed migration and invasion assays of small interfering RNA (siRNA)-targeted ZEB1-transfected cells in vitro. As a result, expression level of ZEB1 was significantly higher in ESCC tissues compared to that in adjacent noncancerous tissues (P < 0.001). High expression of ZEB1 was observed in 55.00 % (55/100) of ESCCs. In addition, high ZEB1 expression was found to be closely correlated with advanced tumor stage (P = 0.001), positive lymph node metastasis (P = 0.001), great tumor depth (P = 0.03), and high histologic grade (P = 0.008). Moreover, multivariate analysis showed that the status of ZEB1 expression was an independent predictor for overall survival in ESCC. Furthermore, knockdown of ZEB1 by transfection of siRNA-ZEB1 abrogated the migration and invasion of ESCC cells in vitro. Taken together, our data offer the convincing evidence that ZEB1 may play a crucial role in promoting aggressive ESCC progression. ZEB1 may serve as an effective prognostic marker and a potential target for therapeutic intervention of ESCC.