Background: Egypt is one of the most affected countries by HCV. Health-related quality of life (HRQOL) has become an important outcome measure in patients with chronic liver disease. Data regarding HRQOL among children patients with chronic hepatitis C (CHC) is lacking. Objectives: To assess the impact of HCV on health related quality of life of chronic hepatitis C children and identify risk factors of HRQOL impairment in those children. Methods: A case control study was conducted on 84 Chronic Hepatitis C Children (CHC) and 124 age and sex matched healthy volunteers. HRQOL was assessed by Child Health Questionnaires (CHQ), The CHQ-Parent Report Form (PF50) and CHQ-Child Report Form (CF87). Risk factors affecting HRQOL of CHC children were assessed by multiple regression analysis. Results: Compared with controls, CHC children had lower HRQOL on all scales of the CHQ. Hypo-albuminemia was significantly associated with impaired physical summary (PhS) of CHQ-Child Form (P= 0.007). However, raised liver enzyme; Aspartate transaminase (ALT) and low platelet count (PLT) were significantly associated with impaired psychosocial summary (PsS) of CHQ-Child Form. Conclusion: CHC children had lower HRQOL than controls. The predictor of impaired Physical HRQOL was hypoalbuminemia while the predictor of impaired psychosocial HRQOL was raised ALT and thrombocytopenia. It is recommended to increase awareness about HCV related issues with special focus on quality of life that is a significant factor when making decisions about hepatitis C treatment strategies. Medical and social support services should be available to children with HCV.