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Purpose: The purpose of the study was to examine the meditating effect of unconditional self acceptance on the relationship between life stress and depression in nursing students. Methods: Data was collected from a survey of 140 nursing students using self-reported questionnaires. The data was analyzed using IBM SPSS Statistic 25.0. The mediating effect of unconditional self-acceptance on the relationship between the subject's life stress and depression was analyzed using Baron and Kenny’s method. In addition, the Sobel test was conducted to determine the significance of the mediating effect. Results: The regression model explained 43% of the variance in nursing students’ depression. Significant factors were task-related life stress, unconditional self acceptance, and academic achievement. Unconditional self acceptance had a partial mediating effect on the relationship between nursing students’ task-related life stress and depression. Conclusion: To prevent depression in nursing students, it is necessary to build effective strategies to manage task-related stress and improve unconditional self-acceptance.