AIMS: This study aimed to determine the mediating roles of perceived control and resilience in the association between mutuality and quality of life (QoL) in caregivers of adults with heart failure. DESIGN: A multi-centre cross-sectional study. METHODS: We recruited 268 patient-caregiver dyads with heart failure using convenience sample enrolled from four hospitals in Henan Province, China from March to December 2023. Caregivers' mutuality, perceived control, resilience and QoL were assessed. A multiple-mediation model was tested using the PROCESS macro in SPSS. RESULTS: Caregivers' mental QoL positively correlated with mutuality, perceived control, and resilience. Caregivers' physical QoL was correlated with mutuality. Conversely, perceived control and resilience showed no significant correlation with physical QoL. Moreover, the association between mutuality and mental QoL was mediated by perceived control and resilience, respectively, and together in series, accounting for 32.3%, 14.1% and 28.2% of the total effect, respectively. CONCLUSION: Perceived control and resilience mediated the link between mutuality and mental QoL in caregivers of adults with heart failure. Interventions targeted at strengthening perceived control and resilience may improve caregivers' mental QoL. Additionally, the mental QoL may be improved by indirectly enhancing mutuality among caregivers of adults with heart failure. IMPACT: It is important to develop multimodal intervention strategies that combine perceived control and resilience to amplify the positive impact of mutuality on the mental QoL of caregivers in individuals with heart failure. REPORTING METHOD: The STROBE guideline was adopted to report this study. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.