ObjectiveThe aim of the present study is to investigate whether parenting stress mediate the relationship between social support and quality of life in parents of children with Autistic Spectrum Disorder. In addition, we examined what other variables moderate the relationships in this mediation model.MethodsUsing the two-stage meta-analytic structural equation modeling approach (MASEM), 44 correlation matrices were synthesized from 28 empirical studies (N = 13,270) and fitted to the hypothesized mediation model.ResultsThere is a significant partial mediation effect of parenting stress on the relationship between social support and quality of life. Subgroup analysis through the first stage analysis suggested that social support measurements, parental role, and child's age moderated the relationship between social support and parenting stress, and that the focus of quality of life moderated the relationship between social support and quality of life. Subgroup analysis through the second stage analysis indicated that parenting stress had a significantly stronger predictive effect on quality of life in Western culture, while the predictive effect of social support on quality of life was significantly stronger in Eastern culture.ConclusionHaving more social support can reduce parents' stress and then improving their quality of life, which can help them cope more positively and effectively with their autistic children.