Background: Asthma causes different physical, emotional, and social limitations for the afflicted children and their families and reduces their quality of life. Therefore, the quality of life in families, particularly in mothers, needs to be enhanced through strategies such as empowerment. Objectives: The aim of this study was to assess the effect of the Family-Centered Empowerment Model on quality of life among the mothers of asthmatic children. Methods: A convenience sample of 172 mothers was recruited for this quasi-experimental study. Mothers were alternately allocated either to a control group or an experimental group based on the day in which they referred to the study setting. Accordingly, mothers who referred to the setting in odd and even days of a weak were allocated respectively to the control and experimental groups. A demographic questionnaire and the pediatric asthma caregiver's quality of life questionnaire (PACQLQ) were used for data collection. The validity of the questionnaire was confirmed by a panel of experts (relevance: 0.98; clarity: 0.96; and simplicity: 0.94) while its reliability was confirmed by a Cronbach's alpha of 0.88. A four-step empowerment program was implemented for the mothers in the experimental group based on the Family-Centered Empowerment Model. The four steps included knowledge improvement, self-efficacy, self-esteem, and evaluation. Mothers in the control group received no intervention during the study. Before and after the intervention, the mothers in both groups were asked to complete the study questionnaires. The data were described and analyzed by using descriptive and inferential statistics. Results: There were no significant between-group differences regarding the mothers' demographic characteristics and their baseline quality of life scores. However, after the intervention, the scores of quality of life and its physical limitation and emotional function domains were significantly lower in the experimental group, denoting higher quality of life (P < 0.001). Conclusions: The Family-Centered Empowerment Model significantly improves quality of life among the mothers of children who suffer from asthma. Given the important role of mothers in giving care to their ill children, nurses are recommended to use the model to encourage mothers' active participation in care giving to their children.