Abstract.Terrein is a bioactive fungal metabolite isolated from Aspergillus terreus. Besides being a melanogenesis inhibitor, previous studies have revealed that terrein has antiproliferative effects on a number of types of cancer tumors. In the present study, the inhibitory effect of terrein on esophageal cancer was evaluated and the possible underlying mechanisms were investigated. The results revealed that terrein inhibited the proliferation of Eca109 esophageal cancer cells in a dose-and time-dependent manner. Mechanistically, terrein treatment led to the G 2 /M phase arrest of Eca109 cells by indirectly regulating cyclin B1 and phosphorylating the cell division cycle protein 2 genes. Notably, terrein exhibited a synergistic effect on Eca109 cells when combined with cisplatin, which is a commonly used chemotherapeutic drug. Taken together, these findings indicate that terrein suppresses the proliferation of esophageal cancer cells, and may prove to be a novel therapeutic approach for the treatment of esophageal cancer via inhibiting the proliferation of cancer cells.