Introduction Adolescents and young adults (AYA) with cancer undergo physical transformations due to disease and treatments occurring alongside puberty and adolescence. Although physical activity is recommended for its benefits, its practice among AYA with cancer remains insufficient. The aim of the Éducation Thérapeutique et Activité Physique: Engagement des Adolescents et Jeunes Adultes atteints de cancer study is to identify the evolution of AYA with cancer medical knowledge and powers (power to act, to express oneself) over life and cancer care, and their role in commitment in adapted physical activity (APA) and therapeutic patient education during and after oncological treatments. Methods and analysis This prospective mixed methods monocentre study will be conducted in a French comprehensive cancer centre. Observations will be conducted two times a week during medical consultations, APA interventions and therapeutic education sessions for AYA with cancer. Semidirective interviews will involve 70 participants, including AYA with cancer aged 15–25, health professionals, APA teachers and parents. Quantitative data will be collected on AYA’s social characteristics and participation in physical activity intervention and therapeutic education sessions. A correspondence factor analysis will supplement inductive analysis of ethnographic qualitative data, involving patient coresearchers. The results will help to improve the understanding of AYAs’ medical knowledge and powers, their commitment in physical activity and to develop strategies to increase their participation. Ethics and dissemination This study complies with reference methodology MR004 of the French National Data Protection Authority and was registered by the Data Protection Officer of the Leon Berard Cancer Center on the activity registry of the institution (Ref. N°R201-004-259; 5 July 2022). Ethics approval has been obtained from the Centre Léon Bérard ethics board (Ref. N°2022–006; 20 July 2022). Oral informed consent will be obtained from all participants before data collection. The results of this study will be published in peer-reviewed scientific journals, national and international conferences.