Aims: The purpose of this study was to test the associations between spiritual needs, perceived social support, spiritual well-being, and quality of life (QoL) and examine the multiple mediating effects of perceived social support and spiritual well-being on the relationship between spiritual needs and QoL among patients with advanced cancer.Methods: Spiritual needs, perceived social support, spiritual well-being and QoL were assessed using self-report questionnaires among 286 cancer patients in a tertiary oncology hospital. The mediation model was analysed using the SPSS PROCESS procedure, and indirect effects were evaluated with bootstrapping.Results: QoL was positively correlated with spiritual needs (r=0.315, p<0.01), perceived social support (r=0.451, p<0.01) and spiritual well-being (r=0.636, p<0.01). The relationship between spiritual needs and QoL was mediated by perceived social support (indirect effect: 0.063, confidence interval (CI) (0.018, 0.118)) and spiritual well-being (indirect effect: 0.068, CI (0.001, 0.155)) and serially mediated by spiritual needs and QoL (indirect effect: 0.072, CI (0.041, 0.113)).Conclusions: The results emphasize the importance of spiritual well-being and social support for cancer patients, especially those with more spiritual needs. They suggest that healthcare providers should develop strategies to enhance perceived social support and spiritual well-being when caring for cancer patients to improve patients’ QoL.