The purpose of this study is to investigate the influences of internal factors (communication method, problematic behavior, functional level, parenting burden in mothers) related to visual impairment and multiple disabilities on the mothers’ health-related quality of life, to provide basic data required for establishment of governmental support plans for the mothers of Visual Impairment students with multiple disabilities. The 146 mothers of students with visual impairment and multiple disabilities attended to 12 visual impairment schools and three living facilities for visually disabled individuals with multiple disabilities were selected as subjects of this study. Conclusions according to the results of this study are as follows. The health-related quality of life on the mothers of students with visual impairment and multiple disabilities is not affected much by internal factors such as communication method, functional level, treatment assistance service, life assistance service, and occupational assistance service of students and marital status of mothers. But it is influenced by parenting burden on the mothers of visual impairment students with multiple disabilities. The parenting burden of mothers is shown the differences across the groups on social capability, emotional limitation, psychological health, vitality, pain, and overall health awareness among sub domains of quality of life. Therefore the parenting burden of mothers have the effect on the mothers’ health-related quality of life, specially on the social capability, emotional limitation, psychological health, vitality, pain, and overall health awareness.