In the present study, we aim to demonstrate, the significance of PI3K/AKT activation in esophageal cancer by examining the p-AKT expression in paired clinical tumor and normal specimens, and to determine the effects of specific inhibitors of PI3K/AKT on caspase-3-dependent cancer cell apoptosis, esophageal tumor growth and chemoresistance by in vitro experiments and in vivo tumorigenesis model. This evidence concerns the gene CASP3 and esophageal cancer.