Background: Hepcidin encoded by HAMP gene plays a key rolein modulating iron absorption in β-thalassemia. Hepcidin deficiency dueto either mutations in HFE gene encoding the hemochromatosis protein(HFE) or in the HAMP gene have been implicated in iron overload.Objectives: A case-control study aimed to verify the influence of G71Dof HAMP gene and H63D of HFE gene variants on iron overload in β-thalassemia major patients. Material & Methods: A total of 52 β-thalassemia major patients and 46 healthy control subjects were screenedfor the H63D and G71D mutations by polymerase chain reactionrestrictionfragment-length polymorphism (PCR-RFLP). Estimation ofiron overload was based on serum iron, TIBC, ferritin and transferrinsaturation. Results: Among the studied patients, 30 (57.7%) carried thewild-type profile, 13 (25%) carried G71D mutation of HAMP gene, 12(23.1%) carried the H63D mutation of HFE gene and 3 (5.8%) carriedboth mutations. Both HAMP-G71D and HFE-H63D mutations observedamong patients were in the heterozygous condition. Patients with eitherHAMP-G71D or HFE-H63D variants did not show significant differencein iron overload parameters in relation to wild-type patients. Conclusion:The G71D mutation of HAMP gene and H63D mutation of HFE gene arecommon among β-thalassemia major patients. Neither the HAMP-G71Dmutation nor the HFE-H63D mutation is a major determinant of totalbody iron status in patients with β-thalassemia major.