BACKGROUND Tislelizumab is an immune checkpoint inhibitor (ICI) widely used in various solid tumors. Nevertheless, immune-related adverse reactions can arise during the administration of this medication. Hypophysitis is a relatively uncommon adverse reaction, typically manifesting as lethargy and hyponatremia. Although ICI-induced hypophysitis is reported, cases presenting with somnolence and delirium are extremely rare. This report describes the case of a 69-year-old woman with advanced endometrial cancer who presented with somnolence, delirium, and eosinophilia after commencing treatment with tislelizumab and was subsequently diagnosed with hypophysitis. CASE REPORT A 69-year-old woman with advanced endometrial cancer, following multiple lines of prior therapy, presented to our hospital with somnolence as the primary symptom. The patient developed worsening daytime somnolence and nocturnal delirium following tramadol administration for pain associated with a metastatic tumor in the left axilla. After a complex diagnostic and therapeutic process, it was determined that the patient had hypophysitis induced by tislelizumab. After receiving hydrocortisone treatment, the patient's symptoms of somnolence and delirium vanished. Two weeks later, the patient once more developed an adrenal crisis following an interventional procedure. We treated her anew with glucocorticoids, and she recovered. CONCLUSIONS This case underlines the necessity for timely assessment of the hypothalamic-pituitary-adrenal axis function in patients presenting with neurological symptoms, such as somnolence and delirium, particularly in the presence of elevated peripheral blood eosinophil counts. Simultaneously, it is essential for us to understand that patients with hypophysitis induced by ICIs require long-term hormone replacement therapy due to adrenocortical insufficiency.