〔Abstract〕 Objective To investigate the inhibitory effect of β-elemene on human esophageal fibroblasts after endoscopic submucosal dissection (ESD) by mediating hypoxia-inducible factor-1α (HIF-1α). Methods Fibroblasts extracted and cultured from esophageal granulation tissue after endoscopic submucosal dissection (ESD) were divided into a control group (conventional culture), and an observation group with different concentrations of β-elemene (160 μmol·L-1, 320 μmol·L-1, 480 μmol·L-1, 640 μmol·L-1 of β-elemene treated ESD fibroblasts), and administered after 0, 24 h, 48 h and 72 h, the growth inhibition rate of fibroblasts was detected by cell proliferation toxicity assay, the apoptosis rate of fibroblasts was detected by flow cytometry, and the expression level of HIF-1α in the control group and 480 μmol·L-1 of β-elemene observation group were detected by protein blotting. Results The proliferation of fibroblasts was inhibited by increasing the concentration of β-elemene, the apoptosis rate of fibroblasts was increased with the increasing concentration of β-elemene, and the expression of HIF-1α was decreased. The level of HIF-1α in fibroblasts transfected with HIF-1α overexpression plasmid was significantly increased, and the increase was reversed by 480 μmol·L-1 β-elemene treatment. Conclusion β-elemene inhibits esophageal fibrosis by mediating HIF-1α levels, attenuating the proliferation of human esophageal fibroblasts and accelerating fibroblast apoptosis.