Patients with hereditary spherocytosis (HS) often require red blood cell transfusions for the treatment of hemolytic anemia. Iron overload is a known complication of frequent transfusions. Deferasirox, an oral iron chelator, can cause transient elevations in serum aminotransferase levels. There have been a few cases demonstrating Deferasirox-associated liver injury in patients with sickle cell anemia and thalassemia. In this case report, we present a 13-year-old male with transfusion-dependent HS treated with Deferasirox who presented with jaundice and was found to have evidence of acute hepatocellular injury.