Previous studies have suggested that insulin-like growth factor binding protein-3 (IGFBP-3) acts as a tumor suppressor in human esophageal squamous cell carcinoma (ESCC). The present study was designed to investigate the clinical and prognostic significance of IGFBP-3 in ESCC patients. In this study, IGFBP-3 was detected by immunohistochemistry (IHC) in paraffin-embedded tissues from 110 ESCC patients, of which 110 were from primary cancer sites and 56 from matched adjacent non-malignant sites. Differences in IGFBP-3 expression and clinical characteristics were compared by χ2 test. Correlations between prognostic outcomes and with IGFBP-3 expression were investigated using Kaplan-Meier analysis and the Cox proportional hazards model. Among adjacent non-malignant tissues, 83.9% of individual tissue staining was scored as either high for IGFBP-3. However, among ESCC cases, only 51.8% of the cancer tissues were scored as high IGFBP-3 expression. In addition, IGFBP-3 expression inversely correlated with pathological classification (P<0.05 for T, N, and M classifications) and clinical staging (P=0.006). Furthermore, patients with higher levels of IGFBP-3 had prolonged overall survival (P<0.001). In conclusion, reduced IGFBP-3 expression may be a risk factor for advanced clinicopathological classification and poor patient survival. These findings suggest that IGFBP-3 may serve as a useful marker for the prognostic evaluation of ESCC patients.