BACKGROUND: A few reports had revealed the clinical associations between hypopituitarism and non-alcoholic fatty liver disease (NAFLD). Further evidences were needed. OBJECTIVES: To report 5 cases of young patients with rapidly progressive NAFLD in conjunction with hypopituitarism, aiming to detect the associations. METHODS: Clinical data of the 5 patients were analyzed retrospectively. All had decompensated liver cirrhosis that was finally attributed to NAFLD. Hypopituitarism was a result of pituitary stalk interruption syndrome in 3 patients and craniopharyngioma in 2. RESULTS: 4 patients were overweight (BMI, 24.2 to 28.4kg/m2). All had insulin resistance (HOMA-IR, 4.8 to 7.2). All suffered from at least one metabolic disorder. All had decompensated liver cirrhosis. The average time duration was 6.9 years between the onset of abnormal liver function and decompensated liver cirrhosis. Fatty liver could be detected in all patients. All had anterior hypopituitarism, and 2 also had posterior pituitary dysfunction. The hormone supplements were insufficient. CONCLUSION: Hypopituitarism may be a rare cause of rapidly progressive NAFLD. Insulin resistance and metabolic disorders caused by multiple hormonal deficiencies may contribute to it. Hormone supplement therapy, especially the growth hormone supplement, should be given at the early age to prevent the severe liver disease.