Purpose: The purpose of this study was to identify factors associated with work-related quality of life (WRQoL) in shift-working nurses. Methods: The design was a cross-sectional observational study. The participants were 187 nurses who were shift-working at C university hospital. Data were collected using structured self-administered questionnaires from December 7 to 31, 2022. The data were analyzed using linear multiple regression. Results: WRQoL in shift-working nurses was borderline between low and moderate (75.35±9.46). Factors associated with WRQoL were job satisfaction (=0.75, p <.001) and quality of sleep (=−0.12, p =.017), and these variables explained 58.4% of the variance in WRQoL. Conclusion: Job satisfaction and quality of sleep should be considered to improve WRQoL in shift-working nurses. Employers or managers should create a supportive organizational climate to maintain family and work balance and to reduce job stress for shift-working nurses. Shift-working nurses are also encouraged to adhere to healthy behaviors for those who are experiencing poor sleep quality.