Studies have demonstrated that physical activities highly promote physical, mental and social health of children and adolescents with autism spectrum disorder. Numerous factors are involved in the lack of participation of this population in physical activities. The goal of this study was to investigate the family barriers to participation of children and adolescents with autism spectrum disorder in physical activities. This descriptive research had an ex-post facto design. The statistical sample comprised 370 Iranian children and adolescents with autism spectrum disorder, from both genders, aged 8 to 20 who were selected via cluster sampling method. The research instrument included a researcher-made questionnaire with Cronbach's alpha of 0.985. Data were analyzed using SPSS23 and Smart PLS3. The results showed that family factors are the barriers to participation of children and adolescents with autism spectrum in physical activities. The component “parents prefer their children to focus more on their school responsibilities instead of physical activity participation.” was reported as the most important barrier and the component "Physical activity takes a lot time from my child and he/she cannot do other family responsibilities and daily activities." was reported as the least important barrier. Due to the significant role of family in children’s physical activity participation, it is suggested that in order to promote the physical activity levels in children and adolescents with autism spectrum disorder, family barriers be considered and strategies be planned to overcome them.