To examine the factors associated with the quality of life and the mediating effect of self-efficacy in the relationship between mental health and quality of life among patients with hypertensive nephrology. A cross-sectional and correlational study using the Strengthening the Reporting of Observational Studies in Epidemiology checklist guidelines. A total of 202 participants were collected from November 2019 to September 2020 from the outpatient department of nephrology of a regional teaching hospital in Taiwan using a convenience sampling method. The research tools included the World Health Organization-5 Well-Being Index, the Chronic Kidney Disease Self-Efficacy Instrument and the Medical Outcome Study Short Form-12. The mediating effect was statistically analysed by linear regression models and verified by Sobel testing. Mental health and self-efficacy were positively correlated with the overall quality of life. The results showed that the total explanatory variation of mental health and self-efficacy on the overall quality of life was 37.1%. Mental health was the most important explanatory factor, which could explain 27.1% of the variations in the overall quality of life alone. Moreover, self-efficacy was a partial mediator in the relationship between mental health and the quality of life among patients with hypertensive nephrology, with a total effect of 34.8%. The quality of life of this population can be improved by enhancing mental health, leading to an improvement in self-efficacy. Consequently, improved mental health and self-efficacy will improve the overall quality of life. Medical staff should be able to assess patients' mental health in providing referrals and assistance in a timely manner. If intervention programmes can be developed to improve patients' self-efficacy, their quality of life can also be improved.