X-linked inhibitor of apoptosis protein (XIAP) is the most potent member of the IAP gene family in terms of its ability to inhibit caspases and suppress apoptosis. In this study, we investigated the expression of XIAP in esophageal cancer tissues and cell lines, and found the elevated expression of XIAP in esophageal cancer tissues compared with normal tissues. Then we used small interfering RNA (siRNA) to block XIAP expression while evaluating the effect of XIAP siRNA on cell apoptosis, and the combined effects with Paclitaxel, Cisplatin, Fluorouracil and Etoposide in XIAP high expression ESCC cell line KYSE150 and EC9706. The results showed that XIAP siRNA efficiently decreased XIAP expression and induced cell apoptosis. Treatment with XIAP siRNA in combination with Paclitaxel, Cisplatin, Fluorouracil and Etoposide enhanced chemosensitivity. These results suggest that XIAP might be helpful for diagnosis of ESCC and XIAP siRNA combined with Paclitaxel, Cisplatin, Fluorouracil and Etoposide may be a feasible strategy to enhance the effects of chemotherapy in patients with ESCC.