The purpose of this study was to explore the relationship between the quality of life (QOL) and feeling of mothers of a child with autism. The QOL instrument was also used. A total of 104 participants completed all questionnaires, which included the Taiwan version of the WHOQOL-BREF. A final robust parsimonious structural model showed a positive correlation between the four domains of QOL. Mother's feeling was positively related to the physical and psychological domains. History of chronic disease was negatively related to mother's feeling and the physical domain. Religion was negatively correlated with the psychological and environmental domains. The study provided evidence that the WHOQOL-BREF is an adequate and appropriate instrument in the assessment of caregivers of children with autism in Taiwan. Mother's feeling, history of chronic disease and religion were related to QOL in these mothers of children with autism.