P>Caspase-3 plays an important role as the key effector during apoptosis, but there are very few studies of caspase-3 in esophageal squamous cell carcinoma (ESCC). The purpose of this study was to investigate the expression and prognostic significance of caspase-3 in ESCC from Linzhou City, a high incidence area in northern China. All 64 patients underwent esophagectomy for ESCC between January 2002 and December were enrolled in this study. Caspase-3 expression was assessed by immunohistochemistry (IHC) in primary ESCC and paired normal esophageal epithelium. The positive rate of caspase-3 expression was higher in ESCC than in normal esophageal epithelium (79.7% vs. 50.0%, Chi-square = 12.372, P = 0.001). Caspase-3 expression was correlated with tumor cell differentiation (Phi = 0.717, P < 0.001), tumor infiltration depth (Phi = -0.334, P = 0.008), and pathologic TNM (pTNM) staging (rs = -0.268, P = 0.032). Patients in caspase-3 positive group had a significantly better 5-year overall survival than those in the negative group (77.4% vs. 35.9%, chi 2 = 7.344, P = 0.007). Our results showed that caspase-3 expression was upregulated in ESCC compared with normal esophageal epithelium in population of Chinese high incidence area, and patients with caspase-3 positive expression had better prognosis. Therefore, caspase-3 immunostaining could be a simple and useful tool for predicting survival in ESCC patients.