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Aim: This study aims to determine health-related quality of life (QoL) and the related factors from the perspective of social determinants of health among children. Background: Childhood is the most intense period of life, and environmental factors surrounding children, as well as individual lifestyle factors, are related to the child's physical and mental well-being. To our knowledge, there is a lack of studies evaluating the relationship between determinants of health and the QoL of healthy children in general. Methods: This cross-sectional study was executed in the Bayrakli district of Izmir city. Stratified clustered sampling was used including 24 schools and 3367 7th-grade children, and 1284 students were targeted (50% prevalence, 95% CI, %5 margins of error, 2.25 design effect, and 20% replacement). The response rate was 84.9% (n = 1090). The Turkish KID-KINDL Health-Related Quality of Life Questionnaire for Children was used to assess QoL. Independent variables were examined in four layers using Dahlgren's Determinants of Health Model: basic characteristics, lifestyle factors, family characteristics, and life conditions. Results: The mean QoL score was 71.3 ± 12.6. Our study explained 31.7% of the variance in QoL. Higher QoL scores were associated with better health status, perceived academic achievement, normal/thin body perception, physical activity (PA), and adequate sleep duration. Living with both parents and having fewer siblings positively influenced QoL. Moreover, the presence of structural problems in the household and poorer health perceptions were associated with lower QoL scores (P < 0.05) This study highlighted the multifaceted nature of QoL in Turkish children, revealing the importance of various determinants of health. The results show that in order to improve the general well-being of this population, interventions and policies are required that concentrate on elements including health status, academic accomplishment, body perception, physical activity, family structure, and living situations. [ABSTRACT FROM AUTHOR]