Sickle cell disease is a congenital condition and its most common clinical manifestation is anemia due to chronic hemolysis. Persistent and accelerated hemolysis associated with multiple transfusions is a recognized risk factor for the development of cholelithiasis. The occurrence of gallstones is one of the most important manifestations of sickle cell disease in the digestive tract. Most gallstones are pigmented and characteristically occur at younger ages and the prevalence of cholelithiasis increases progressively with age, affecting 50% of young adults. Cholecystectomy is the most common surgical procedure performed in sickle cell disease patients. Anesthesia in this population of patients for major surgeries deserves special attention due to various complications particularly silent infarctions of end organs are common. We are reporting a 14-year-old girl diagnosed with sickle cell anemia and β(+) thalassemia with cholelithiasis went for cholecystectomy under general anesthesia. Although the patient has both β(+) thalassemia and sickle cell disease component, the latter is of more concern for anesthesia.