Context. The use of positive and negative spiritual coping has been demonstrated among patients with cancer and their family caregivers. However, the dyadic effects of family caregivers and patients with advanced cancer on spiritual coping, as well as the factors associated with spiritual coping, remain unclear. Objectives. To identify the dyadic interactions and factors associated with spiritual coping among patients with advanced cancer and their family caregivers in China. Methods. This was a multicenter cross-sectional study conducted in four tertiary hospitals. The participants were 326 dyads of patients with advanced cancer and their family caregivers. A demographic information questionnaire and the Spiritual Coping Hope Index, and Perceived Social Support Scale were used to examine study variables from January to May 2023. The ActorPartner Interdependence Model was used to explore the dyadic effects of spiritual coping. Results. The APIM showed that patients' depression, spiritual health, and social support had actor effects on their spiritual coping, while family caregivers' self-efficacy had a partner effect on patients' spiritual coping. Additionally, family caregivers' self-efficacy, anxiety, and depression had actor effects on their spiritual coping, while patients' self-efficacy, anxiety, and spiritual health had partner effects on family caregivers. Conclusion. Spiritual coping is a dyadic phenomenon in patients with advanced cancer and family caregivers. Improving self-efficacy, spiritual health, and social support, as well as addressing symptoms of anxiety and depression, can enhance spiritual coping abilities and consequently improve quality of life. J Pain Symptom Manage 2025;69:483-495. (c) 2025 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.