Purpose: The purposes of this study were to investigate the relationship between stress, spirituality and quality of life and verify the effect of mediating spirituality in the relationship between stress and quality of life among nursing students. Methods: A total of 173 fourth-year nursing students who have experienced clinical practice participated in this study. Data were collected using structured questionnaires to measure the stress, spirituality and quality of life in nursing students from November 9 to December 9 in 2020. Data analysis was conducted using independent t-test, ANOVA, Pearson’s correlation coefficient, and mediated regression analysis of Baron and Kenny. Results: The results show that stress were negatively correlated with quality of life (r=-.49, p<.001) and spirituality (r=-.40, p<.001). In addition, spirituality was positively correlated with quality of life (r=.56, p<.001) and had a partial mediation effect on the relationship between stress and quality of life. Conclusion: The results of this study indicate that in order to reduce stress and improve the quality of life of nursing students, it is necessary to actively apply a spirituality promotion program recognizing and developing nursing student’s spirituality.