Introduction: The burden of care and fear of disease progression is noticeable in mothers of children with cystic fibrosis. Hence, this study was done with the aim to determine the relationship between the burden of care and fear of disease progression in mothers of children with CF. Method: 142 mothers of children with CF participated in this correlational study. Data were collected with the sequential method. The -The self-report Zarit burden of care and fear of disease progression questionnaires were Used. Results: According to the results, the mean maternal burden of care was 34.12 ± 69.77, and the mean fear of disease progression was 32.12 ± 92.11. The burden of care had the highest regression effect on fear of disease progression in mothers of children with CF (β = 0.896). With an increase of one unit of standard deviation in the burden of care, an increase of 0.896 units occurred in fear of disease progression in parents of children with CF. Discussion: Mothers of children with CF experience a moderate burden of care and fear of disease progression. An increase in the burden of care and psychological stress increases the fear of disease progression in these mothers. It is recommended that healthcare providers, especially nurses, consider the conditions of this group of mothers due to the burden of care and long-term fear of disease progression and plan and implement appropriate care interventions.