Empowering HD patients to solve their own problems and take responsibility for managing their illness and its associated problems or complications through a problem solving approach, education and support based on an individual patient’s needs and shared goal setting can lower the limitations of providing the same protocol for all. There is a lack of sufficient literature to support the effectiveness of empowerment programs on QoL, clinical and laboratory indicators in HD patients. This is noteworthy in the context of Iranian culture and particularly regarding HD patients, thus this study aims to investigate the effect of empowerment on self-care self-efficacy, QoL, and clinical and laboratory indicators in a group of Iranian ESRD patients.