Background: The population of individuals with end-stage renal disease (ESRD) in Korea is increasing rapidly, yet comprehensive research on the quality of life (QOL) of this population undergoing hemodialysis is scarce. Purpose: The purpose of this study was to identify the factors influencing QOL of Korean hemodialysis patients with ESRD. Methods: This study was a cross-sectional survey. Data were drawn from a convenience sample of 141 patients aged 918 years receiving maintenance hemodialysis in a general hospital. Data were collected by a self-administrated survey conducted from June 15 to July 25, 2012. The questionnaire included basic subject data, QOL, fatigue, perceived health status, and emotional status. Results: The meanQOL scorewas 3.09 or ‘‘above average’’ as measured by the World Health Organization’s (1993) Quality of Life Assessment. Significant differences were observed for basic subject data including educational level, occupation, monthly income, medical expense assistance, and family living situation. Significant negative correlations were found between QOL and fatigue and between anxiety and depression, but a significant positive correlation was found with perceived health status. The factors influencing QOL were fatigue and depression, marital status (married), and medical expense assistance (from self or parents). Conclusions/Implications for Practice: The results of this study indicate that, to improve the QOL in patients with ESRD, comprehensive intervention is necessary to assess and manage depression and fatigue. Social mediation is needed to enhance the QOL of patients with ESRD who lack familial and economic support, those who are single, or those who cannot afford medical expenses either by themselves or with the help of their parents.