The aim of this study was to determine the relationship between spirituality and hopelessness in cancer patients. The study used a cross-sectional and correlational design and included 650 cancer patients. The data were collected using a patient information form, the Spiritual Orientation Scale, and the Beck Hopelessness Scale. The data were analyzed by MANOVA and linear regression analysis. Cancer patients had high levels of spirituality (89.74 ± 32.79) and low levels of hopelessness (6.50 ± 5.61). A statistically significant relationship was found between the mean Spiritual Orientation Scale scores of the patients and their sociodemographic characteristics (sex, age, marital status, educational status, employment status, income) (p < 0.05). A statistically significant relationship was found between the mean Beck Hopelessness Scale scores of the patients and their sociodemographic characteristics (age, marital status, income status) (p < 0.05). According to the linear regression analysis, a significant negative correlation was found between the spirituality and hopelessness levels of the patients (p < 0.01, R 2 = 0.503, b = − 0.641). As the patients' spirituality increased, their levels of hopelessness decreased.