Abstract: Objective: To explore the effect of SP600125, a specific c-jun NH 2 terminal protein kinase (JNK) inhibitor, on apoptosis and Caspase-3 activation of the human esophageal cancer cell lineEca-109 induced by the COPADG. and to discuss the possible molecular mechanisms in COPADG-in-duced apoptosis. Methods: The human esophageal caner cell line Eca-109 was cultured in vitro and was incubated with SP600125 and COPADG. The Changes in the expression of P-JNK was determined with immunofluorescence cytochemistry, apoptosis rate and Caspase-3 activity was analyzed using flow cytometry. Results: SP600125 remarkably reduced the expression of P-JNK and decreased apoptosis rate as well as Caspase-3 activity in the human esophageal cancer cell line Eca-109 compared with those treated with COPADG only. Conclusion: SP600125 has a significant inhibitory action on Cas-pase-3 activation and indirectly demonstrate a significant protective effect on the COPADG- induced apoptosis in Eca-109. Thus, JNK signaling pathway may play an important role in apoptosis of Eca-109 induced by the COPADG.