Objective <p>This study aimed to explore the real experiences of family adjustment and adaptation of children with acute leukemia in China, and to identify the influencing factors, which will provide a basis for the development of family-centered intervention strategies in the future.</p> Methods <p>This study is a descriptive qualitative study. Semi-structured interviews were conducted between September to December 2024 with parents of children with acute leukemia in a general hospital. Fifteen eligible participants were recruited using purposive sampling. Data were analyzed using thematic analysis.</p> Results <p>A total of fifteen parents of children completed the interviews. From the interview data, four themes and eleven subthemes emerged from our inductive analysis: (1) The cumulative effects of multiple pressures; (2) Effective activation and synergistic empowerment of protective resources; (3) Meaning construction and cognitive adaptation and (4) Adaptive responses to risk factors. The combination of multidimensional resources, positive cognitive appraisals, and coping styles build a solid foundation for families of children with acute leukemia to effectively cope with multiple stresses and dilemmas.</p> Conclusion <p>The process of adjustment and adaptation in families of children with acute leukemia is complex and dynamic, influenced by stressors, resources, cognitive appraisals, and coping styles. This study confirms the applicability of the dual ABC-X model in explaining the family dynamic adjustment process among children with acute leukemia, providing a potential pathway for developing individualized clinical interventions.</p> Reporting Method <p>This study followed the COREQ checklist</p>