Chronic liver disease can cause an increase in portal sinus pressure, which may lead to rupture and bleeding of esophageal and gastric varices. Oesophageal variceal ligation, with use of sclerosing agent and tissue glue injection is commonly used in clinical practice to address oesophageal bleeding. A 58-year-old male patient with chronic liver disease was treated with oesophageal variceal ligation, sclerosing agent and tissue glue injection due to oesophageal and gastric variceal bleeding. After 2 days, the skin of the patient exhibited erythema to different degrees. After 10 days of dexamethasone treatment, the whole-body rash worsened, and a severe skin reaction appeared that was suggestive of toxic epidermal necrolysis (TEN). Strict mucosal care was provided, and corticosteroids, γ globulin and adalimumab were concurrently used for treatment. After 20 days, the patient recovered from the skin problems. To the best of our knowledge, TEN after endoscopic surgery has rarely been reported in the relevant literature. Furthermore, when patients being treated with multiple drugs have erythema multiforme, physicians should be alert to the possibility of its development into TEN. The present case report summarizes the treatment methods for patients with TEN, providing a practical clinical basis and direction for the future diagnosis and treatment of the condition.