Background/Aim. Although long-term survival of childhood cancer patients is significantly improved, prolonged treatment and hospitalization might have negative impacts on child development. The aim of this study was to verify profile of health-related quality of life parameters in population of schoolchildren during hospitalization and treatment for malignant disease. Methods. The Serbian version of Pediatric Quality of Life Inventory Version 4.0 (PedsQLTM4.0) Generic Core Scales was applied. A total of 120 schoolchildren were analyzed: 60 patients hospitalized for prolonged malignant disease treatment and 60 healthy schoolchildren from public schools. The study was done at the Institute for Oncology and Radiology of Serbia, as well as in four schools. Results. Generally, schoolchildren hospitalized for cancer treatment demonstrated lower scores on physical, emotional, social and school functioning when compared to healthy schoolchildren from regular public schools. Significant differences were observed for all the 8 items of the Physical Health Scale, in 2 out of 5 items of the Emotional Functioning Scale, in 4 out of 5 items of the Social Functioning Scale, and 3 out of 5 items of the School Functioning Scale. Conclusions. The Serbian version of PedsQLTM 4.0 Generic Core Scales could be successfully used to evaluate physical, emotional, social and school functioning of hospitalized children and adolescent. Schoolchildren hospitalized for prolonged tumor treatment have poorer HRQOL scores compared to general healthy population, however the level of remaining physical, emotional and social parameters should provide solid foundation for their potential rehabilitation, education and inclusion.