OBJECTIVE: This study investigated whether psychological flexibility, the key construct in the Acceptance and Commitment Therapy (ACT) model of psychological and behavioural change, significantly predicts wellbeing and functioning in people living with and beyond cancer. DESIGN: This was an online, prospective, longitudinal, correlational study with two time points that were approximately three months apart. METHODS: All participants were required to be at least 18 years of age, be in cancer remission and resident in the United Kingdom. Recruitment for Time-point 1 (n = 331) took place from May to July 2023 and Time-point 2 (n = 266; 80% retention rate) took place between Sept and Nov 2023 using Prolific (an online recruitment platform). The mean age was 51.65 (SD = 13.99). The mean length of remission in months was 89.45 (SD = 80.59) and mean years since diagnosis was 8.91 (SD = 6.99). Data were analysed cross-sectionally and longitudinally. Covariates adjusted for included age, years since diagnosis, time in remission, ethnicity, cancer type and cancer stage. RESULTS: Cross-sectional hierarchical regression analyses showed Time-point 1 psychological flexibility significantly (at p < .001) predicted anxiety, depression, stress, fatigue interference, fear of cancer recurrence, quality of life and pain interference. Psychological flexibility at Time-point 1 significantly predicted all psychosocial variables at Time-point 2, while adjusting for confounding variables. CONCLUSIONS: The findings show that psychological flexibility predicts key psychosocial outcomes relevant for people in remission from cancer. This study provides evidence for the relevance of psychological processes targeted in ACT-based interventions in the context of people living with and beyond cancer.