Background: Diagnosing a child with cancer has devastating physical, mental, and psychosocial consequences on the child’s life as well as the whole family. It is estimated that two hundred thousand children and adolescents suffer from different types of cancer worldwide yearly, with the majority living in low and middle-income countries which translates to a high mortality rate in these countries. Objective: This study aims to evaluate health-related quality of life among children with different chronic conditions and make a comparison among them. In addition, the study will draw a comparison between children’s perspective about their quality of life and parents’ perspective. Furthermore, the study will address the associations between quality of life with disease severity, duration and the presence of other co-morbidities. Methods: This was a prospective, analytical, correlational study design in which Pediatric Quality of Life Inventory (PedsQL 4.0 generic core scale) was administered to assess quality of life on 110 children; 50 children with cancer, 30 children with thalassemia and 30 children undergoing hemodialysis. Researchers interviewed children as well as their parents. Results: Results showed that children with Thalassemia had the lowest scores and suffered from poor quality of life compared to the other two groups of children. Interestingly, quality of life level among children undergoing dialysis was lower than children with cancer. However, there were marked discrepancy between child’s and parents’ answers on scale questions. The level of quality of life, in all children, were statistically significant in relation with family size, income and parents’ education. Conclusion: We identified high prevalence of poor level of health-related quality of life among children included in this study. The findings support that the quality of life among children with chronic conditions should receive more attention in our local medical settings.