The purpose of this research was to compare healthy individuals with patients having primary brain tumors (PBTs) with respect to their psychological hardiness and spirituality. In this study, a comparative and descriptive research design was employed. The research sample included 122 individuals: 61 patients with PBTs and 61 healthy individuals. When healthy individuals were compared with patients with PBTs, it was found that the patients with PBTs had significantly lower mean scores for spirituality and psychological hardiness. The study revealed that spirituality (beta = .661) and age (beta = - .270) were statistically significant predictors of psychological hardiness (p < .001). These variables explained 53% of the total variance. To decrease the negative effects of PBTs on psychological hardiness, nurses and other health staffs should focus on strategies that strengthen patients' spirituality.