Purpose: Caring for a child with cerebral palsy (CP) can impact both the physical and mental health of parents. However, determinants associated with health-related quality of life (HRQOL) in these parents have yet to be adequately examined. The study aims were to identify the determinants affecting HRQOL among mothers of children with CP. Design and Methods: Participants in this cross-sectional study (N = 180) were mothers of children with CP recruited from clinical and school-based settings in Korea. Variables examined were characteristics of child (demographic factors and disability parameter), mother (demographic factors, number of chronic conditions, health-promoting behaviors (HPB), and parenting stress), and environmental factors (use of personal assistant care, leisure time and social support). Multivariate regression analysis was performed to examine the child, mother, and environmental factors associated with HRQOL. Results: The HRQOL results revealed that the physical HRQOL was higher than mental HRQOL in the sample. Longer length of disability of children and lower number of chronic conditions of mothers were significant factors of higher physical HRQOL. Lower parenting stress, more leisure time, engagement in HPB, and greater social support were significantly associated with higher mental HRQOL. Conclusions: The levels of HRQOL of mothers of children with CP were very low and our findings suggest modifiable factors. Decreasing parenting stress, engaging in HPB, and providing social support should be considered when developing psychosocial intervention for this population. Practice Implications: Study results may inform programs aimed at health promotion, stress reduction, and QOL improvement among parents of children with disabilities. (c) 2018 Elsevier Inc. All rights reserved.