Introduction nephrotic syndrome (NS) is a common glomerular disease in children. The long relapsing nature of the disease along with medication-related complications can affect all aspects of the life of the affected children. This study points to estimate the health-related quality of life (HRQOL) in Sudanese children with NS. Methods this case-control questionnaire-based descriptive study included 100 children with NS aged 2-18 years and 100 healthy children. HRQOL was assessed using the Arabic copy of the Pediatric Quality of Life Inventory Generic Core Scales (PedsQL™ 4.0 GCS). Results most of the patients were males (64%) and 17% were steroid resistant. Mean PedsQL™ 4.0 summary and domains´ scores in NS were significantly lower than controls (p≤ 0.05 for all) except for the social domain (p=0.266) with the lowest patients´ scores being for school functioning (mean ± SD, 74.4 ± 26.4). The QOL scores considerably differed between the various clinical phenotypes of NS with patients in the initial episode (N=25) having considerably lower total, school, and social domains scores compared to other clinical types (p=0.027, 0.017, 0.006 respectively). Conclusion this study assesses for the first time the QOL in Sudanese children with NS. Sudanese children with NS had lower life quality scores in comparison to healthy children and need tireless efforts to improve their lives. PedsQL™ 4.0 scale is simple and can be used in everyday clinical practice to evaluate QOL in children with NS.