Introduction: Inability in self-care in children with autism can severely affect different aspects of mothers' lives, especially coping and quality of life. The aim of this study was to evaluate the relationship between autistic children's self-care performance and mothers' coping and quality of life. Material and methods: This was a cross-sectional study. 110 mothers and their autistic children were selected via convenience sampling. Three questionnaires were completed by participants. Data were analyzed by SPSS software version 16. Results: There was a strong and direct correlation between self-care performance and coping of mothers and mothers' quality of life (p < 0.001). The variables of coping, quality of life, autistic child's age and gender, number of siblings, level of function, mothers' education and job predicted approximately 70.65% of self-care performance variation. Conclusions: Children with autism had fairly good self-care performance, which had a positive effect on adaptation and consequently quality of life of their mothers. Self-care performance promotes the coping and quality of life in mothers of children with autism. Therefore, health officials and policymakers are recommended to use the findings of this study to increase coping and quality of life in these mothers, improve their self-care performance, and pay attention to this point in clinical practice.