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Background: This study aims to explore the association between the quality of life (QoL) in children with Down syndrome (DS) and its relationship with demographic characteristics of both parents and children. The investigation encompasses five domains: physical and psychological well‐being, autonomy and parental relationship, social well‐being, and peers, as well as school and the learning environment. Method: An online questionnaire, the KIDSCREEN‐27, was used to measure the QoL of 112 families with DS in Saudi Arabia, referred to as "Parent‐Reported Measures." Descriptive statistics were analyzed using the Statistical Package for Social Sciences. Results: The study found that the QoL of children with DS showed high scores in the psychological well‐being, autonomy, parental relations, school, and learning environment domains. However, the physical and social well‐being and peer domains had lower scores, although still considered "good scores." Family income had a positively significant influence on all QoL domains. Specifically, higher family income was associated with better QoL outcomes, except for social well‐being. Parental age was found to influence psychological well‐being, while parental education and the relationship between the parent and child influenced social well‐being. Lastly, the child's gender was found to have an impact on the school and learning environment domain. Conclusion: The study highlights the importance of understanding the impact of the demographic variability of children with DS and their parents on the QoL of their children. It emphasizes the need to address the needs of families with lower incomes and the importance of parental education and relationships with their children in improving social well‐being. The findings could aid policymakers and healthcare providers in improving the QoL for families with children who have DS. This study aims to determine the relationship between demographic variables of parents with down syndrome (DS) children and their quality of life (QoL). It is the first time to use the Arabic version KIDSCREEN questionnaire, after validation. This is the first study to measure the demographic variables influence on the reported QoL of children with DS. This study found that family income influenced all QoL domains except social well‐being. Psychological well‐being was influenced by parental age. Social well‐being was influenced by parental education. Finally, the school and learning environment was influenced by the child's gender. [ABSTRACT FROM AUTHOR]