Employing in vitro and in vivo ESCC‐induced cachexia model, we found that protein disulfide isomerase inhibitor, CCF642, prevented cisplatin‐induced apoptosis of myoblasts, myotube atrophy and ameliorated cachectic features in vivo, including muscle and adipose tissues wasting and inflammation. The gene discussed is P4HB; the disease is esophageal squamous cell carcinoma.