Objectives: To create basic data for developing nursing intervention protocols to increase the quality of life (QOL) of children with rare diseases and caregivers by comparing the health-related QOL of both. Methods: A questionnaire was used to assess the QOL of patients and caregivers. The data were analyzed using the t-test, ANOVA, and multiple regression analysis. Results: Children with rare diseases and caregivers were rated as having less psychosocial (mental) health related QOL than physical health related QOL. The physical component summary (PCS) of the caregivers was not related to QOL of the children with rare diseases. The mental component summary (MCS) of the caregivers was positively affected with the emotional function (nursing care diseases: β=0.072, p=.001; medical care diseases: β=0.197, p<.001) of the children. Conclusions: Relative to their rare diseases, caregivers generally reported that their child was more impaired, which suggests the need for multiple social supports. These points should be kept in mind when assessing and treating children with rare diseases and their families as psychological interventions that target areas of concern (e.g., coping with having a rare disease) may be helpful for improving child and caregivers QOL.