One of the most prevalent hereditary hemoglobinopathies worldwide is ????-thalassemia. Finding out how certain apoptosis genes (Casp-8 and Casp-9) affect erythropoiesis in patients with β-thalassemia major was the aim of this investigation. This study involved 60 patients with β-thalassemia major, according the age the highest percentage of incidence in group (21-30) years with percentage (60%), depending on the sex; the results recorded there were (53.35%) of male patients and (46.65%) female patients. The analysis of complete blood count parameters revealed a significantly decrease in red blood cell count was observed in BT patients (4.091 ±0.04×10⁶/μl) compared to controls (5.951 ±0.08 ×10⁶/μl), the hemoglobin levels (HGB) were significantly lower in BT patients (10.99 ±0.11 g/dL) compared to controls (15.88 ±0.366 g/dL), the mean corpuscular volume was significantly lower in BT patients (61.28 ± 5.20 fL) compared to controls (90.86±4.20 pg). White blood cell (WBC) showed significantly increase in patients with B-thalassemia (12.03 ±1.06 x 103/ μl) compared to control (8.28 ±0.22 x 103/μl) and the Platelets levels are significantly higher in thalassemia patients (373.64 ±21.01 x 103 μl ) compared to healthy control group (279.18 ±9.02 x 103 μl). The quantitative analysis of RT-PCR of Casp-8 and Casp-9 genes showed significantly increase in patients (4.38) and (3.58) respectively compared to healthy control (1.00). In conclusion; the overexpression of the Casp-8 and Casp-9 genes are significantly affected erythropoiesis, which will reflect in a better knowledge of the pathophysiology of β-thalassemia major disease. This disease's inefficient erythropoiesis is caused by the overexpression of Casp-8 and Casp-9 genes that linked to apoptosis.