Background: Serum Hepcidin level drop is a main feature of chronic hemolytic anemia like β-thalassemia as an example. It is assumed that Hepcidin is influenced by anemia, iron overload due to repeated blood infusions and inflammation due to iron disposition in tissues. Aim of the study: To measure plasma levels of the iron regulatory hormones; hepcidin and GDF-15 in β-thalassemic patients during intravenous blood infusion in order to assist clinical monitoring. Patients and Methods: 30 cases previously diagnosed as a βthalassemia major (group I) and 20 normal individuals of the same age and gender group (group II). The samples were collected immediately before and 8 days after transfusion. Hepcidin and GDF-15 levels were estimated using ELISA kit that is commercially available. Results: As regard to serum Hepcidin level in both control and patient group was similar before the transfusion. The hepcidin level increased significantly after transfusion in both groups but in was significantly higher in patient group. Hb and hepcidin increased significantly posttransfusion. The pre-and post-transfusion hepcidin showed significant correlation with Hb, Iron, and Ferritin in thalassemia patients. The pretransfusion Growth Differentiation Factor-15 was shooting in cases with β-thalassemia than presumably healthy control. The GDF-15 level decreased significantly after transfusion and it was significantly correlated with Hb and hepcidin levels. Conclusion:Hepcidin serum level assessment can be used to monitor patients with iron-loading anemia and identify the patients prone to iron overload complications and iron toxicity.