A case of severe immune-related colitis complicated by spontaneous transanal passage of necrotic intestinal mucosa following immune checkpoint inhibitor therapy is reported. The patient was diagnosed with stage IV thymic squamous cell carcinoma and was treated with albumin-bound paclitaxel and carboplatin in combination with tislelizumab. At 5.5 weeks after the last cycle of combined chemotherapy and immunotherapy, colonoscopy revealed scattered mucosal congestion, erosions, and superficial ulcers throughout the colorectum. Subsequently, an approximately 20-cm-long segment of dark-red necrotic intestinal mucosa was discharged through the anus. Histopathological examination of intestinal mucosal biopsy specimens supported the diagnosis of immune-related enterocolitis, which was classified as grade 3 according to the Common Terminology Criteria for Adverse Events. Conservative treatment, including bowel rest, nutritional support, mucosal protection, and symptomatic management, resulted in no significant clinical improvement. Following multidisciplinary consultation involving the departments of gastroenterology, colorectal surgery, and oncology, the necrotic intestinal tissue was surgically removed. The patient recovered uneventfully after the procedure. Histopathological examination of the resected tissue demonstrated ischemic necrosis of the intestinal mucosa accompanied by a severe inflammatory response. This case highlights the complexity and diversity of the clinical manifestations, diagnosis, and management of immune checkpoint inhibitor–related colitis. For patients receiving immune checkpoint inhibitors who develop hematochezia or diarrhea, early assessment and grading of colitis, repeated clinical evaluation, and prompt multidisciplinary consultation are recommended. When necrotic tissue is identified or conservative treatment is ineffective, timely surgical intervention should be considered to prevent serious adverse outcomes.