Background: Esophageal cancer is a digestive tract malignancy, ranking sixth among the world's deadliest tumor incidence. However, the pathogenesis of esophageal cancer is complex and the prognosis remains poor. Therefore, in-depth study of the pathogenesis and developing effective treatments are of great value for esophageal cancer. beta-elemene is a natural monomeric compound derived from the Chinese herbal Curcuma wenyujin. beta-elemene has been reported to have anti-tumor effects and used as an adjunct to clinical therapy for multiple cancers. This study aims to explore the effects of beta-elemene on esophageal cancer and its related molecular mechanisms. Methods: TE-1 and KYSE-150 cells were used to evaluate the activity of beta-elemene on esophageal cancerin vitro and in vivo. Western blot was performed for protein expression assessment. CCK8 assay and cell cycle analysis were used for proliferation testing. Flow cytometry was performed for apoptosis detection. Wound healing assay was subjected to assess the migration ability. Transwell chamber assay was applied to assess the invasion ability. HE staining, TUNEL staining and immunohistochemical staining were used to evaluate the changes in tumor tissues. Results: We found that beta-elemene treatment suppressed proliferation, as well as induced apoptosis of esophageal cancer cells. In addition, beta-elemene inhibited the migration and invasion ability of esophageal cancer cells. Furthermore, beta-elemene exerted its effects against esophageal cancer by specifically regulating AKT signaling, thereby controlling the expression of PD-L1. Conclusion: beta-elemene inhibits proliferation and metastasis of esophageal cancer cells by regulating the phosphorylation of AKT.