Background: Thalassemia affects not only child's life, but also leaves psychological, social, and economic burdens on their parents. So, health coaching assist mothers toward disease-focused and child's health promotion. Aim: The study aimed to evaluate the effect of health coaching intervention on mothers' performance and quality of life of their children with beta-thalassemia. Methods: A quasi-experimental research design was used. Setting: This study implemented in the Inpatient Pediatric Department at Mustafa Hassan Hospital affiliated to Fayoum University. Sample: Non-probability purposive sampling that consisted of 70 mothers and their children with Beta thalassemia recruited from the above-mentioned setting. Tools: Four tools were used pre /post health coaching intervention. Tool (I): A structured interviewing questionnaire to assess mothers' knowledge related to thalassemia and coaching. Tool (II): Coaching practices rating scale. Tool (III): Mothers practices observational checklists. Tool (IV): Quality of life inventory version 4.0 for children. Results: There was a highly statistically significant improvement appeared between the studied mothers' knowledge and practice as well as quality of life of their children with beta-thalassemia at pre and post coaching intervention. Conclusion: Implementation of mothers' health coaching intervention improved mothers' knowledge, practices, and the quality of life of their children with beta-thalassemia. Recommendation: The health coaching intervention for mothers of children with thalassemia should be used in all hospitals that provide care for children with thalassemia.