ABSTRACTBackground and aim:The pathogenesis of β-thalassemia has been attributed to ineffective erythropoiesis. The function of Hox genes in normal haematopoiesis has been widely studied using gene expression analysis. The aim of this study is to evaluate the expression of HoxA9, and HoxA5genes in beta-thalassemia.Materials and methods:Children with thalassemia major, thalassemia intermediate, and age and sex-matched healthy controls (n = 50/group) were enrolled. Detection of HoxA5and HoxA9mRNA expression was performed by real-time polymerase chain reaction (RT-PCR).Results:Expression of HoxA9increased in a direct linear trend (median 0.5 in controls, 2.4 in intermediate disease, 4.1 in major disease, p = 0.001) and generally correlated with the red cell count, haematocrit, ferritin and levels of beta-globin. In those with thalassemia major, the relative change of HoxA9was linked to transfusion history, the white blood cell count, ferritin, and beta-globin (all r > 0.5, p < 0.001). Levels of HoxA9were superior to HoxA5in differentiating controls from thalassemia intermedia, whilst both differentiated major from the intermediate disease.Conclusion:This study highlights the importance of HoxA genes in early identification of patients, at high risk of developing complications, as it allows specific measures to delay the progression of the disease. HoxA gene expression is a promising diagnostic and prognostic marker in patients with β-thalassemia.