Nodular regenerative hyperplasia of the liver (NRHL) is an uncommon non-malignant finding typically associated with haematological or auto-immune disease. The main clinical symptom is portal hypertension in the absence of underlying liver cirrhosis. The pathogenesis of NRHL remains unknown. We report a case of NRHL with cholestasis and progression to liver insufficiency without any underlying disease and no association with systemic disease or drug intake. Cholestasis and liver function tests improved significantly during treatment with ursodeoxycholic acid (750 mg per day). Based on this case, it may be concluded that treatment with ursodeoxycholic acid might be beneficial in patients with NRHL and progression to liver insufficiency.