Background Insulin-like growth factor-binding protein-3 (IGFBP-3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma (ESCC). The present study was designed to investigatethe clinical and prognostic effects of IGFBP-3 on ESCC.Methods: IGFBP-3 was detected by immunohistochemistry in paraffin-embedded tissues from 70 ESCC patientstreated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissuesand adjacent non-malignant esophageal specimens. Receiver operating characteristic (ROC) analysis was used todetermine cut-off scores for tumor positivity and to evaluate patient survival status. The χ2 test was performed toanalyze the association of IGFBP-3 expression with clinical characteristics and radiotherapy response. Associationsbetween prognostic outcomes and IGFBP-3 expression were investigated using Kaplan-Meier analysis and the Coxproportional hazards model.Results: The threshold for IGFBP-3 positivity was set to greater than 65% [area under the ROC curve (AUC) = 0.690,P 〈 0.019]. Of the 70 ESCC patient tissues tested, 32 (45.7%) were defined as having high IGFBP-3 expression. Thelevels of IGFBP-3 protein expression were decreased in 70.0% (7 of 10) of ESCC tissues compared with adjacent nonmalignantesophageal tissue. In addition, IGFBP-3 expression was associated with pathologic classification (P 〈 0.05for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP-3 in the tumor had animproved radiotherapy response and prolonged overall survival (P 〈 0.001).Conclusions: High level of IGFBP-3 expression in ESCC associates with early clinical stages and are predictive forfavorable survival of the patients treated with radiotherapy.