© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.Our aim was to determine impairments in physical functions, activity limitations, and participation restrictions with the International Classification of Functioning, Disability and Health version for Children and Youth (ICF-CY) framework in children with acute lymphoblastic leukemia (ALL) receiving treatment. Physical functions were assessed in terms of pain level, fatigue level, handgrip strength, and motor proficiency. Fine motor activities and lower extremity performance were assessed to determine activity limitations. Participation was assessed with a patient-reported questionnaire. Thirty children with ALL (mean age: 8.45 ± 3.33 years) were included. Pain and fatigue level were mild. Poor handgrip strength was found; their mean handgrip strength was 60% of the normative. Fifty-six percent of the children had below-average motor performance. Participation scores were considerably high, except for sport and physical functioning sub-score. Participation level was positively associated with bilateral coordination and duration after diagnosis, while negatively correlated with pain and fatigue level (p ˂ 0.05). Conclusion: The ICF-CY-based evaluation was useful to understand children’s limitations in everyday life. Children with ALL need supportive interventions during treatments in terms of physical functioning and participation in activities. Children with ALL with higher pain and fatigue, poor bilateral coordination, and who were in earlier period after diagnosis had higher risk for participation restriction.What is Known:• Children with ALL had physical functioning limitations on treatments.• Participation restrictions were described in children with ALL off treatment.What is New:• The ICY-CY-based health and functioning evaluation allows health care professionals to globally determine limitations of everyday life in children with ALL on treatment.• Impairments in physical functions, pain severity, fatigue severity, and duration after diagnosis are associated with participation to everyday life in children with ALL on treatment.