<p>Objective: The aim of this study was to evaluate the health instructions effect on quality of life and psychological problems among children with thalassemia.<br />Design: Quasi-experimental design used in this study. Pre and post evaluation done to identify the effect of health instructions sessions which provided by the researchers for thalassemic children and their parents on children heath related quality of life and psychological problems using Pediatric quality of life inventory PedsQL 4.0 generic core scale which was used to measure health-related quality of life in children and adolescent. In addition, Depression, Anxiety and Stress Scale (DASS) used to evaluate psychological problems among children.<br />Setting: It was conducted at outpatient and hematological unit affiliated to Beni-Seuf University hospital. <br />Sample: The total children included in this study were 23 children of either sex, aged (7-18y). Children with physical or mental handicapped excluded from the study.<br />Results: The results of this study showed that more than two third of studied children scored medium level in physical and school function. As well as, there was no significant differences in thalassemic children health related quality of life domains post health instructions sessions where p &gt; 0.05. Also these study findings demonstrated that 60% of children had extremely sever anxiety and 43.5% of them had severe depression. However, post health instruction sessions these findings showed statistical significant decline where p value = .001 and .000 respectively.<br />Conclusion: An important finding to emerge in this study is studied children with thalthemia had psychological problems with poorer health related quality of life. However, the results set out to the provision of health instructions for children with thalthemia and their parents had significant effect in improvement of children psychological problems. Unfortunately, there is no significant effect in their health related quality of life post instructions sessions. Thus, the results of this study suggest that the importance for the continuous heath educations program providing for thalassemic children and their parents by pediatric and psychiatric nurses. In addition, health team collaboration for monitoring psychological problems of children with thalassemia and assist children and their parents to more adjustment in their health related quality of life.</p>