• Magnolol inhibits esophageal carcinoma cell proliferation and induces autophagy in a dose- and time-dependent manner.
• Magnolol upregulates HACE1 expression at the transcriptional level, leading to increased LC3-II and autophagy.
• HACE1 knockout abolishes magnolol's anti-proliferative and autophagy-inducing effects, confirming HACE1's essential role.
• The HACE1-OPTN axis is identified as a novel mechanism for magnolol's antitumor activity, suggesting its potential as a therapeutic agent for esophageal carcinoma.