Update publication information. Esophageal cancer is the seventh most common cancer in the world. Although traditional treatment methods such as radiotherapy and chemotherapy have good effects, their side effects and drug resistance are still obvious. The repositioning of drug function provides new ideas for the research and development of anticancer drugs. We previously identified a Food and Drug Administration (FDA) approved drugsulconazole can effectively inhibit the growth of esophageal cancer cells, but its molecular mechanism is not clear. Here, our study demonstrated that sulconazole had a broad spectrum of anticancer effects. It can not only inhibit the proliferation, but also inhibit the migration of esophageal cancer cells. Both transcriptomic sequencing and proteomic sequencing showed that sulconazole could promote various programmed cell death and inhibited glycolysis and its related signal pathways. Experimentally, wefound that sulconazole induced apoptosis, pyroptosis and ferroptosis. Mechanistically, sulconazole triggered mitochondrial oxidative stress, inhibited glycolysis and activating BCL2/Bax/Caspase3 axis. Finally, we discovered that low-dose sulconazole canincrease radiosensitivity of esophageal cancer cells. Taken together, these new findings provided strong laboratory evidence for the clinical application of sulconazole in esophageal cancer.