Health-related quality of life is a useful and important clinical measure in children with end-stage renal disease for monitoring their well-being; the hemodialysis (HD) nurse has an effective role in achieving this approach. Aim of this study was to evaluate the impact of range of motion exercise program for hemodialysis nurses on quality of life for children with end-stage renal disease undergoing hemodialysis therapy. The study utilized a quasi-experimental design. It was conducted at Adult and Pediatric Hemodialysis Units in Benha University Hospital. The sample included 32 nurses working at the previously mentioned settings and 34 children undergoing HD therapy. Data were collected through the following tools; the first tool: a structured interviewing questionnaire tool for nurses which included: nurses’ characteristics, assessment of nurses' knowledge regarding HD and range of motion (ROM) exercise, nurses' attitude toward application of ROM exercise program. The second tool was an observational checklist to assess nurses’ performance regarding ROM exercise for children undergoing HD. The third tool involved: a) children' characteristics, b) Pediatric Quality of Life Inventory™ Version 4.0 scale. The study results concluded that, there were improvements in total mean scores of nurses’ knowledge, performance and attitude after program implementation toward ROM exercise. As well as, there were statistically significant differences between the mean scores of children’s QOL before and after implementation of ROM exercise program. The study recommended the integration of ROM exercise program in the routine care of children undergoing hemodialysis therapy.