Pharmacologic stimulation of fetal hemoglobin (HbF) expressionmay be a promising approach for treatment of β-thalassemia. The aim of the present study was to determine the effect of a histone deacetylase inhibitor Apicidin on HbF production in β thalassemic-cultured erythroid precursor cells. The study was conducted on twenty five β-thalassemic patients. Patients were selected from Hematology clinic of El Mounera children Hospital, Cairo University. Erythroid precursors derived from peripheral blood were grown in 2-phase liquid culture system modified after El-Beshlawy et al., 2008. In this procedure, early erythroid progenitors proliferate and differentiate during phase 1 (in the absence of erythropoietin) into late progenitors. In phase 2, in the presence of erythropoietin, the latter cells continue their proliferation and mature into Hb-containing orthochromatic normoblasts. Apicidin was added on the days 4 to 5 of phase 2 (when cells started to synthesize Hb), and cells were harvested on day 12. Induction of HbF was analyzed by alkaline denaturation method.The percentage of HbF production increased from 18.06 ±11.38% inuntreated cultures to 56.93 ± 27.46 %. The Mean of Hb F % wassignificantly higher in Apicidin treated cultures than in untreated cultures, p.value is 0.0001 and this difference is considered to be of high statistical significant. The fold increase of Hb F in Apicidin treated cultures ranges from 1.35 to 17.7, with a mean of 4.34 + 3.65. There was a positive correlation between HbF% in untreated cultures and apicidin treated cultures (correlation coefficient 0.665) and this correlation is considered to be of moderate significance. There was a negative correlation between the fold increases of HbF% in Apicidin treated cultures and HbF% in iii untreated cultures (correlation coefficient -0.532) and this correlation is considered to be of moderate significance. The results indicated an increased HbF in cultures of all samples studied (increased in 100% of cases). These results are of potential clinical significance because an increase of HbF alleviates the symptoms underlying β-thalassemia. The results of this study suggest that Apicidin warrants a further evaluation as a potential therapeutic drug for treatment of β-thalasemia.