Background: The study objectives are to measure the quality of life among children with cancer compared to healthy peers and to determine factors affecting the QOL among those children. Methods: Analytic cross sectional study was conducted in Sohag National Cancer Institute in Sohag Governorate for children with cancer and a comparison group of healthy peers. Threre were 3 tools were used for this study: Demographic questionnaire, Socio-economic scale, and Peds QL4.0 Generic Core Scale had to measure HRQoL. Results: All items of QoL: physical, emotional, social, school, psychological and total QL scores were lower among the cancer patients group than the control group with very high statistical significant difference. The mean total QoL score was 70.9 ± 13.3 among the cancer group versus 94.2 ± 2.4 for the healthy peers. Males represented 47.1% of the studied group versus 52.9% for females. Other QoL functions showed no statistical significance difference regarding disease duration. Conclusions: cancer is negatively affecting all the QOL functioning of the children. We recommend that Integrated programs between child's home, school and National Cancer Institute for educating and supporting children with cancer to improve their HRQOL. Key Words: Health-Related Quality of Life, National Cancer Institute