Introduction: Sickle cell disease (SCD) causes chronic hemolysis which is a risk factor for cholelithiasis. Its development may lead to severe and life-threatening complications. Objective: Determine the prevalence of cholelithiasis, the conditions of diagnosis and related factors. Materials and Method: We retrospectively reviewed records of 110 patients with sickle cell disease followed up in Charles de Gaulle University Pediatric Hospital from January 2003 to December 2013, including 103 patients who had abdominal ultrasonography. Results: Cholelithiasis prevalence was 24.3%. The mean age of patients was 10.8 years, (range 3 to 15 years). Sex ratio was 2.1. In 88% cases, cholelithiasis was diagnosed based on the characteristic symptoms of right hypocondrial pain, fever and icterus. Most factors associated with cholelithiasis were as follows: age above 10 years (OR = 4), occurrence of at least three (03) vaso-occlusive crises per year (OR = 7.6), history of blood transfusion (OR = 8), right hypochondrial pain (OR = 4.5) and icterus (OR = 15). Only 20% of patients suffering from a symptomatic cholelithiasis underwent laparoscopic cholecystectomy and results were conclusive. Conclusion: Patients with sickle cell disease, especially those aged above 10, should be routinely tested for cholelithiasis using abdominal ultrasonography at least once a year. Because of the difficulties in managing evolutive complications in case of an emergency in our context, we advocate laparoscopic cholecystectomy of any cholelithiasisas soon as it is diagnosed in children with sickle cell disease.