This work clearly revealed that the combination therapy with cDDP and CEH had synergistic cytotoxic on ESCC, and the combination treatment stimulated apoptosis through downregulation of anti-apoptotic Bcl-2, upregulation of apoptotic Apaf-1, P21 and p53 expression, activation of the c-Jun/JNK signaling pathway, inhibition of P-gp expression, and reduction of the pumping of cDDP from ESCC cells to increase the accumulation of cDDP in tumor cells and increase tumor cells sensitivity to cDDP. The gene discussed is MAPK8; the disease is esophageal squamous cell carcinoma.