Objective To investigate the quality of life in children with osteogenesis imperfecta in southwest China， and analyze the influencing factors， and to provide a reference for the management of this disease at home. Methods A mixed methods design was employed to study the quality of life of children with osteogenesis imperfecta. In the qualitative phenomenological research part，we conducted semi-structured interviews with 20 osteogenesis imperfecta caregivers from a tertiary class-A children's hospital，and used Colaizzi's seven-step method to analyze the interview data. In the quantitative research part，we used the Pediatric Quality of Life Inventory to assess the quality of life of 34 children with osteogenesis imperfecta in southwest China，and determined the influencing factors through univariable and multivariable linear regression analyses，with age-matched healthy children as the control group. Results Five themes were identified in the qualitative research about quality of life：worry about fractures，a high pain tolerance，a lack of walking aids， a lack of peer communications，and a friendly school atmosphere. The quality of life of children with osteogenesis imperfecta was lower than that of healthy peers，with significant differences in the total score（t=-6.732，P<0.001），the physiological function score（P<0.001），and the social dimension（P<0.001）. Independent walking ability（t=3.490，P=0.001） and fixed playmates（t=3.164，P=0.003） entered the multiple regression equation，which co-explained 40.9% of variations in the quality of life score. Conclusion Family's disease management ability is needed to improve the quality of life for children with osteogenesis imperfecta. Medical staff need to establish chronic disease management at home from the aspects of knowledge popularization， medical guidance， future planning， and avoiding potential problems.