Background: The focus of recent research has significantly shifted from explaining the causes and symptoms of autism to investigating issues related to the parents of autistic children. Objectives: This study aimed to investigate health-related quality of life (HRQOL), depression, and associated factors among parents of autistic children in Kermanshah, Iran. Methods: In this cross sectional study performed in 2015, a total of 97 male and female parents of autistic children completed 3 questionnaires: background/demographic checklist, 36-item short-form health survey (SF-36), and beck's depression inventory. Data were analyzed using SPSS version 18. Results: Analysis of the general physical health domain of HRQOL demonstrated no significant difference between men and women (P > 0.05). On the other hand, in all subdomains of mental health, women's scores were higher in comparison with men, and there was a significant difference in the mental health domain. Also, analysis of depression level revealed that 25.8% of the subjects had severe depression. Conclusions: Given the low level of QOL and depressive symptoms in more than two-thirds of parents of autistic children, psychological empowerment of this group is recommended.