Background <p>Cognitive late effects are a common and serious complication of childhood cancer. This risk is particularly high in preschool-aged children, who are in a critical period of cognitive development and thus more susceptible to cognitive late effects. However, interventions targeting cognitive late effects in preschool children with cancer remain scarce and lack a strong evidence base.</p> Objective <p>This study aimed to explore the acceptability and feasibility of Cognifit, an innovative digital gamified cognitive training method, in improving cognitive late effects among preschool children aged 3–6 years with cancer, and to describe the determinants of its implementation.</p> Method <p>A single-group, pre–post embedded mixed-methods design was employed to evaluate the feasibility, acceptability, adherence, and preliminary effectiveness of CogniFit among preschool children with cancer. Feasibility, acceptability, and adherence were assessed using quantitative indicators and qualitative caregiver interviews. Preliminary effectiveness was evaluated using the Behavior Rating Inventory of Executive Function–Preschool Version (BRIEF-P), Sustained Attention Test, Working Memory Test, and Pediatric Quality of Life Inventory Version 4.0 (PedsQL™ 4.0). Quantitative and qualitative findings were integrated for analysis.</p> Result <p>Eighteen children and their caregivers were enrolled in the study; two participants withdrew, and 16 dyads were included in the final analysis. Quantitative findings demonstrated good feasibility and acceptability, with an intervention completion rate of 88.9%, session attendance rate of 81.7%, and duration adherence rate of 72.9%. Qualitative interviews showed that caregivers generally perceived the CogniFit program positively despite challenges related to regular participation and cultural adaptation. Preliminary effectiveness outcomes warrant further evaluation in larger controlled trials.</p> Conclusion <p>Our study confirmed the feasibility and acceptability of the Cognifit digital gamified intervention for preschool-aged children with cancer and their caregivers. The study underscores the importance of adapting digital gamified interventions to better suit vulnerable populations such as preschool-aged children with cancer and proposes corresponding improvement recommendations. Future research should explore modifications to the intervention protocol while conducting large-scale, multicenter randomized controlled trials to evaluate the effectiveness of the intervention.</p> Trial registration <p>Chinese Clinical Trial Registry ChiCTR2400092143 <a href="https://www.chictr.org.cn/showproj.html?proj=229415">https://www.chictr.org.cn/showproj.html?proj=229415</a>.</p>