Hemodialysis is one of the treatment modes for end stage renal disease patients. ESRD and dialysis affect the daily lives of many patients and families confronted by changes in health status, lifestyles, and roles. This study was conducted to assess QoL exhibited by these patients and factors affecting it. Descriptive exploratory design was used. A purposive sample of 100 adult undergoing HD was recruited from two renal insufficiency and dialysis units at hospitals in Cairo. Interviewing schedule questionnaire and Kidney disease quality of life (KDQoL-SF™) tools were used. Findings indicated that QoL of patients undergoing HD was significantly impaired, numerous clinical and socio-demographic factors were found to have significance difference but the most powerful predictors are psychosocial factors. To conclude identifying and understanding QoL of these patients and its determinant factors are fundamental aspect to help health care providers especially nurses to establish methods that would help patients to lead more productive lives, designing and implementing nursing interventions according to patients' needs and fears, thus continuous monitoring and evaluating is recommended.