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Purpose: Numb is evolutionary conserved from Drosophila to human, and considered as the cell fate determination protein by being asymmetrically segregated during cell division.Mammalian Numb (mNumb) displays a complex pattern of functions in fields such as developmental neurobiology and cancer biology.However, little is known about the role of Numb in esophageal squamous cell carcinoma (ESCC),which is the predominant histological type of oesophageal carcinoma with an increasing incidence and poor prognosis in Asian populations.In this study, we focused on the expression, biological functions and preliminary mechanism of Numb in ESCC.Methods: Tissue microarray and immunohistochemisty was performed to evaluate the expression of Numb in ESCC tissues and corresponding non-cancerous tissues.Westem Blot was also performed to confirm the expression of Numb in ESCC tissue and cell lines.Long term follow-up and Kaplan-Meier survival analysis were used to the prognosis of ESCC patients after operation.Analysis Flow Cytometric Analysis and MTT test were performed to evaluate the influence of Numb on the apoptosis and proliferation of ESCC cells.Results: Our study found that Numb was significantly upregulated in ESCC tissues compared with corresponding non-cancerous tissues using tissue microarray.Kaplan-Meier survival analysis suggested that the higher expression of Numb was significantly associated with high tumor recurrence (p=0.015) and poor post-operative overall survival (p=0.016).The expression of Numb was an independent predictor of poor prognosis with a multiple Cox regression.Knockdown of Numb in ESCC cell lines using siRNA effectively inhibited the proliferation and increased the apoptosis of the ESCC cells.Conclusion: Our study strongly indicates that Numb might act as an oncoprotein here and represent a novel prognostic biomarker and therapeutic target for patients with ESCC.