Duchenne muscular dystrophy results in a broad spectrum of physical and psychosocial consequences, both to patient and caregivers. This study was aimed to explore health-related quality of life and its possible determinants in Duchenne muscular dystrophy children and in their parents. Caregivers (21 mothers and 6 fathers; mean age, 40.04 years) of 27 Duchenne muscular dystrophy patients (mean age, 11.26 years) completed the validated Children Health Questionnaire-Parent Form 50 and the Family Strain Questionnaire. Children reported significantly lower scores than normative group in 10 of 15 Children Health Questionnaire dimensions. Only the use of wheelchairs (P = .02) and ventilators (P < .001) was significantly associated to lower health-related quality of life in Physical Functioning. On the contrary, Family Strain Questionnaire scores were not influenced by children's characteristics. Despite the presence of Duchenne muscular dystrophy deeply impairs health-related quality of life, some areas of well-being are present both in children and caregivers.