Esophageal cancer represents the fourth most common gastrointestinal cancer and generally confers a poorprognosis. Prostaglandin-producing cyclo-oxygenase has been implicated in the pathogenesis of esophageal cancergrowth. Here we report that prostaglandin dehydrogenase, the major enzyme responsible for prostaglandindegradation, is significantly reduced in expression in esophageal cancer in comparison to normal esophagealtissue. Reconstitution of PGDH expression in esophageal cancer cells suppresses cancer cell growth, at least inpart through preventing cell proliferation and promoting cell apoptosis. The tumor suppressive role of PGDHapplies equally to both squamous cell carcinoma and adenocarcinoma, which enriches our understanding of thepathogenesis of esophageal cancer and may provide an important therapeutic target.