Background: The incidence and prevalence rates of end‐stage renal disease in Taiwan rank among the highest in the world. The quality of life of these patients deserves close attention.Purpose: The purposes of this study were to explore the relationships among biological functions, symptoms, functional status, general health perceptions, and health‐related quality of life in patients undergoing regular hemodialysis at a regional teaching hospital in central Taiwan.Methods: A cross‐sectional descriptive correlational study design was conducted and 137 valid questionnaires were collected. The 5 structured questionnaires used to collect data included the Biological Function, Symptom Scale, Karnofsky Performance Scale, General Health Perceptions Scale, and the World Health Organization Quality of Life (WHOQOL) scale. Date was analyzed using SPSS 20.0 software.Results: Study results found a mid‐range score for WHOQOL. Symptoms correlated negatively with WHOQOL, while functional status and general health perceptions correlated positively with WHOQOL. Participant symptoms, functional status, general health perceptions, and duration of hemodialysis were the important predictors of WHOQOL, explaining 53.5% of WHOQOL variance.Conclusions / Implications for Practice: Having fewer symptoms, better functional status, and better general health perception correlated with higher WHOQOL scores. Symptoms, functional status, and general health perception were significant predictors of WHOQOL. Health professionals must focus greater attention on the health perceptions of their patients and treat patient symptoms and compromised functional status as early as possible in order to improve quality of life.