Objective <p>The burden of care experienced by carers of cancer patients during the patient's lengthy medical treatment seriously affects their mental health and quality of life. Although social support may play a moderating role in this relationship, its specific role remains to be elucidated. This study aimed to investigate the mediating role of care burden in the relationship between psychological resilience and quality of life, as well as the moderating role of social support.</p> Methods <p>329 primary caregivers of cancer patients were chosen for the study from a tertiary hospital in Jinzhou, Liaoning, China, using a convenience selection technique. Data were collected using the Psychological Resilience Scale (CD-RISC), Carer Burden Inventory (CBI), Quality of Life Scale (SF-12), and Social Support Scale (SSRS). Additionally, descriptive statistics were utilized to study the sample.</p> Results <p>Significant correlations were found between psychological resilience, burden of care, social support, and quality of life of primary caregivers of cancer patients (<i>P</i> &lt; 0.01). Mediation analyses showed that psychological resilience was a significant predictor of quality of life and that the effect of psychological resilience on quality of life was mediated to some extent by the caregiving burden.</p> Conclusions <p>Care burden mediates the relationship between psychological resilience and quality of life, and social support moderates the relationship between care burden and quality of life. A high level of social support can reduce the level of caregiver burden and enable caregivers to maintain a high level of living standards. Primary carers of cancer patients are physiologically and psychologically vulnerable during the long process of treatment and care of cancer patients, and their overall level of quality of life should also be taken seriously, with clinical practitioners paying timely attention to their overall health status and providing appropriate and timely interventions and tools.</p>