Abstract:  To investigate the role of adenomatous polyposis coli ( APC ) in esophageal squamous cell carcinoma ( ESCC ) development and progression and to explore the association of APC with the clinicopathological characteristics and five-year survival of ESCC patients. Methods: A total of 236 formalin-fixed, paraffin-embedded esophageal tumors and the corresponding normal epithelia were placed in a tissue microarray. Using tissue array and immunohistochemistry, the expression of APC was determined in the 236 ESCC tissues and their corresponding normal esophageal mucosal tissues. The correlation of APC expression with age, gender, tumor cell differentiation, lymph node metastasis, tumor-node-metastasis stage, general classification, and five-year survival rate of ESCC patients was analyzed. Results: APC protein expression was confined to the cytoplasm of ESCC cells. ESCC tissues had a significantly lower APC down-expression rate than the corresponding normal esophageal tissues ( 32.2% vs. 92.9%, P < 0.05 ). The APC down-expression was correlated with the tumor/metastasis/node stage ( P = 0.002 ), but not with the age, gender, tumor cell differentiation, lymph node metastasis, or general classification ( P > 0.05 ). Survival analyses showed that the abnormal expression of APC was associated with the five-year survival rate of patients with ESCC. Conclusion: APC down-expression may play an important role in the progression and development of ESCC, generally leading to a lower survival rate. Hence, APC has prognostic value, and is a potential therapeutic target of ESCC.