Background: Hepatobiliary involvement in patients with chronic hemolytic anemia is multifactorial and ranges from benign hyperbilirubinemia to potentially hepatic failure and cirrhosis. Aim and methods: a cross- sectional observational study aimed at the assessment of the prevalence of different forms of hepatobiliary disease among 100 Egyptian children with hereditary chronic hemolytic anemia (45 B-thalassemia, 40 sickle cell anemia, 15 hereditary spherocytosis), and to clarify its features and its possible underlying risk factors. Results: symptoms of hepatobiliry dysfunction included abdominal pain in 53%, hepatic symptoms in 58%, and biliary symptoms in 41%. Sixty-six percent patients had elevated AST level, 47% had elevated ALT and 58% has elevated total bilirubin. Fifty-two patients had abnormal coagulation profile and 21% of 61 subjects were HCV seropositive with hepatomegaly being the only predictor of HCV seropositivity. The prevalence of colelithiasis was 21% and 10% had biliary sludge. Cholithiasis correlated significantly with frequency and duration of transfusion. Multivariate logistic regression analysis showed that abdominal symptoms, hepatomegaly, and prolonged PT/PTT could predict biliary stones. Hepatomegaly detected in 73% patients and multivariate logistic regression analysis showed that abdominal and hepatic symptoms, prolonged PT/PTT and biliary stones could be predictors of hepatomegaly. Conclusion: In conclusion, the main features of hepatobiliary disease are hepatomegaly, gall stones and hepatitis C virus infection. Hepatobiliary complications are frequent findings among children with chronic hemolytic anemia supporting the need for clinical and ultrasonographic follow up for early detection and treatment of these complications.