Sickle cell/β (+) thalassemia (Hb S/β (+)thal) is considered as a variant form of sickle cell disease. Acute episodes of vasoocclusive pain crisis are characteristic for sickle cell disorders and may be complicated by an acute or chronic life-threatening organ dysfunction. Chronic intrahepatic cholestasis is a rare and severe complication in sickle cell disease, characterized by marked hyperbilirubinemia and acute hepatic failure with an often fatal course. Despite the fact that patients with Hb S/β (+)thal usually have a mild type of disease, herein we describe an interesting case of chronic intrahepatic cholestasis with successful outcome in an adult patient with Hb S/β (+)thal.