To conclude, our report described for the first time the down regulation of IGFBP5 that conferred CDDP resistance in ESCC and the potential role of restoring the CDDP sensitivity in ESCC cells through increasing the expression of IGFBP5. This approach offers the potential prospect of overcoming cisplatin-resistance if the work can be extended to the other human cancer types as the approach of gene therapy in future. This evidence concerns the gene IGFBP5 and esophageal squamous cell carcinoma.