Aim: The present study aimed to examine the relationship between self-compassion and cognitive empowerment with quality of work life, emphasizing the mediating role of health anxiety among nurses employed in hospitals in Sabzevar during the first half of 2025. Methods: The research method was descriptive-correlational with a structural equation modeling approach. The statistical population consisted of all nurses working in hospitals in Sabzevar during the first half of 2025, from whom 290 individuals were selected through convenience sampling. Data were collected using standardized questionnaires on self-compassion (Reis et al., 2011), cognitive empowerment (Nejati, 2013), quality of work life (Walton, 1973), and health anxiety (Salkovskis et al., 2002). Data analysis was performed using Pearson correlation tests and structural equation modeling in Statistical Package for the Social Sciences version 22 and Analysis of Moment Structures version 22. Results: The findings indicated that both self-compassion (r = 0.25, p < 0.01) and cognitive empowerment (r = -0.13, p < 0.05) were significantly associated with quality of work life. Moreover, bootstrap results confirmed that health anxiety played a significant mediating role in the relationships between self-compassion (B = 0.04, p < 0.05) and cognitive empowerment (B = -0.14, p < 0.01) with quality of work life. Conclusion: The results of this study provide a foundation for designing psychological interventions and educational programs aimed at improving quality of work life and reducing health anxiety in hospital settings.