Research on resilience helps parents promote health-related quality of life (HRQOL) and mitigate stress associated with raising a child with disabilities. Therefore, understanding how resilience works for parents to inform future interventions and services is important. However, the mutual relations among parental stress, family resilience, and parents' HRQOL for families of children with autism spectrum disorders (ASD) have not been investigated in the literature. This study examined the associations among these three variables for these families and would benefit the parents as well as their children. A sample of 1003 parents of children with ASD reporting both parents' HRQOL from a national dataset was included in this study. This dataset surveyed parents who had a child aged 0-17 in the household in the United States. The investigated latent variables were constructed by the items selected from the survey. Results showed that parental HRQOL could be directly affected by parental stress beta = - 0.19, p <.001 and family resilience, beta = 0.31, p <.001. Parental stress could be directly affected by family resilience, beta = - 0.29, p <.001. Parental HRQOL could be indirectly affected by family resilience through parental stress, beta = 0.055, SE = 0.013, p <.001, 95% CI = 0.034 to 0.084. In conclusion, family members could rely on and share the burden and responsibility for each other to increase their family resilience, which could assist parents to reduce their parental stress and directly and through the reduction of their parental stress indirectly increase their HRQOL.