Objective: In paediatric oncology, little is known about trajectories of illness perceptions and their longitudinal associations with health-related quality of life (HRQoL). Therefore, the aim of this study was to investigate changes in illness perceptions in children and parents over a one-year-period and to investigate predictive value of child's and parent's illness perceptions during acute treatment for child's HRQoL 1 year later. Methods: N = 65 child-parent-dyads participated in a longitudinal study (retention rate: 80.2%). Children were 4–18 years of age and underwent acute cancer treatment at baseline. Children and parents reported on their own illness perceptions (Illness-Perception-Questionnaire-Revised), as well as on the child's HRQoL (KINDL-R) at baseline and one-year-follow-up. Paired-samples t-tests were calculated to investigate changes over time. A hierarchical multiple regression analysis was performed to investigate predictive value of child's and parent's illness perceptions for child's HRQoL. Results: Child's HRQoL t(63) = −6.73, p < 0.001, their perceptions of coherence (i.e. understanding; t(54) = −2.36, p = 0.022) and consequences of their illness (t(54) = 2.86, p = 0.006), and parent's perception of cyclical trajectory (t(61) = 2.06, p = 0.044) improved from baseline to 1-year-follow-up. All other illness perceptions remained stable. Exploratory post-hoc analyses showed differences in the pattern of change in age-, gender-, and diagnosis-specific subgroups. After controlling for baseline levels of HRQoL, child's perceptions of symptoms and consequences were independent predictors of their HRQoL 1 year later (R ² = 0.396, F(2,52) = 10.782, p < 0.001), whereas no parent's illness perceptions added predictive value. Conclusion: In paediatrics, child's and parent's illness perceptions should be assessed. Our findings highlight the importance of illness perceptions as potential modifiable variables in interventions to improve child's HRQoL.