Background: Spiritual health is considered one of the most important components of health and palliative care that facilitates harmonious and integrated communication among one's inner forces. One of the basic principles of holistic nursing care is to pay attention to the spirituality and spiritual care of patients. Spiritual care is an important source of adaptation in refractory and chronic patients such as cancer. Objectives: The aim of this study was to determine the effect of spiritual care on the spiritual health of adolescents with cancer. Methods: This pre-experimental, single-group, pre-post study was performed on 35 adolescents with cancer admitted to Imam Ali Teaching Hospital in Zahedan from May to September 2019. Convenient sampling technique was performed to carry out the study based on inclusion criteria. Data collection tools included demographic information questionnaire and Paloutzian and Ellison Spiritual Health questionnaire. Before and after the spiritual care intervention, the required data were collected by interviewing adolescents and using questionnaires. The data were analyzed using Shapiro-Wilk test and paired t-test. Results: Adolescents' overall spiritual health score increased from 52 ± 7.34 before the intervention to 102 ± 6.57 after the intervention and the difference was significant (P = 0.001). Conclusions: According to the findings of the present study, spiritual care is effective in the spiritual health of adolescents with cancer and can promote adolescent spiritual health. Therefore, it is suggested that nurses incorporate spiritual care into their patient care plans as a simple, accessible, safe and affordable way to promote their spiritual health.