Pediatric acute liver sickle crisis, also known as sickle cell intrahepatic cholestasis (SCIC), is an uncommon but fatal complication of sickle cell disease observed mainly in patients with homozygous sickle cell anemia. Herein we describe a case of pediatric SCIC treated successfully with manual exchange transfusion (ET). The patient was admitted for jaundice, enlarged liver and signs of hepatic failure, such as hyperbilirubinemia and coagulopathy. There was no evidence of viral hepatitis or biliary obstruction. We performed a session of ET in order to reduce the percentage of Hb S to level inferior to 30% which was successfully accomplished. The patient had complete recovery of hepatic function. This case has shown that ET is an effective treatment of pediatric SCIC and should be introduced early on the onset of this severe complication.