β-Thalassemias are due to β-globin gene mutation leading to the absence or reduction of β-globin chains formation. Numerous studies are showing the rising of oxidative stress in β-thalassemia major patients. The study aims to evaluate the effects of N-acetylcysteine (NAC) on total oxidant status and Hb levels in children with β-thalassemia major. This study is a randomized clinical trial in the department of pediatrics, Beni-Suef University during the period between May 2019 and October 2019. The subjects of the study were beta-thalassemia major, the study was conducted on 44 patients that were divided into two groups, 22 patients took NAC at a dose of 10 mg/kg (solvymist syrup or, NAC sachet) orally, for 3 months, and the second group as a non-treatment group. Article results show a significant increase in HB for the treatment group between form the first measurement until the 3rd month. There was a significant decrease between Total Oxidant Status before and after three months in the treatment group. Therefore, NAC may be effective in reducing serum Total oxidant status and increase pre-transfusion Hb levels in children with β-thalassemia major.