Abstract Background:  b-thalassemia is acommon haemolytic anae-mia in Egypt. Renal complicationsare an underestimated problem of b-thalassemia. Renal injury has been attributed to the anaemia, the haemolysis, iron overload, or iron chelators. ApoE gene polymorphism has been studied in many settings in b-thalassemia. Aim of Study: In our study, we aimed to examine the possible relation of ApoE gene polymorphism to renal disease in b-thalassemia patientsand whether the APO E4 allele can be a potential genetic risk factor for the development of proteinuria in that population. Patients and Methods: Forty patients with b-thalassemia were recruited from the Internal Medicine outpatient clinic at the Kasr Al-Ainy Hospital, Cairo University and compared to 45 healthy control subjects, age and sex-matched. b-thalassemia patients were further subdivided in two group. Group I with ACR less than 30mg/mg (20 patients) and group II with ACR more than or equal 30mg/mg (20 patients). ApoE Polymorphisms genotyping was performed by Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP). Results: Our results showed that there was a statistically significant difference between cases and control regarding serum creatinine, eGFR and ACR. The distribution of ApoEin b-thalassemia cases is E2/E3 10%, E3/E3 87.5% and E3/E4 2.5% and in control is E2/E3 4.4%, E3/E3 88.9% and E3/E4 6.7% with a statistically significant difference (p-value <0.001). Conclusion: Our study demonstrated a significant differ-ence in eGFR, Albumin Creatinine Ratio and ApoE genotyping between b-thalassemia cases and control. Although the distri-bution of ApoEin b-thalassemia cases is statistically different from control, it was not correlated to eGFR or proteinuria.