Objective To deeply explore the factors influencing physical activity behaviors in children with acute leukemia, and to provide references for developing clinical intervention programs. Methods A purposive sampling method was used to select 12 children with leukemia and their parents. A descriptive qualitative research approach was employed, utilizing semi-structured interviews. Thematic analysis was conducted to organize, analyze, and refine the data. Results Three themes and nine subthemes were derived based on the Capability，Opportunity，Motivation-Behavior (COM-B) model:capability factors (partial loss of physical function, lack of knowledge related to physical activity), opportunity factors (multichannel external support, environmental and facility resource support, personalized exercise prescriptions and guidance), and motivation factors (perceived value of participation in physical activity, self-efficacy in physical activity participation, preferences for physical activity, and influence of surrounding role models). Conclusion The factors influencing physical activity participation during the treatment period in children with leukemia are diverse. Healthcare professionals should focus on children′s exercise experiences and preferences in clinical practice, employ diversified health education, utilize evidence-based medical concepts, leverage emerging mobile technologies to enhance children′s motivation to participate, and improve the social support system. This approach encourages children to develop regular physical activity habits, improving their disease outcomes and quality of life.