Purpose: The purpose of this study is to investigate factors affecting the quality of life in the mothers of children with disability and to identify the relationships between mother's quality of life, self-efficacy, social support and parenting-stress. Methods: The subjects were 160 mothers of children with disabilities in G city. The data were collected using a structured questionnaire and analyzed with SPSS/PC+ 21.0. Results: There was a significant relationship between mother's quality of life and self-efficacy (p<.001), and their quality of life and social support (p<.001). Mother's Quality of life was negatively correlated with parenting stress as well (p<.001). Variables affecting their quality of life were self-efficacy, social support, parenting-stress and the income of families with children with disability. The four factors accounted for 38.7% of the quality of life. Conclusion: The results of the study show that self-efficacy, social support and parenting-stress are the most significant factors affecting mother's quality of life. It is urgently needed to develop nursing intervention that will enhance mothers' quality of life, thereby helping them to lead a more decent life.