This study evaluated the associations between economic, social, psychological factors, and health-related quality of life of hemodialysis patients. Cross-sectional study design was used. End-stage renal disease patients who had received maintenance hemodialysis for more than 2 months at 14 centers in northern Taiwan were invited to participate. Demographic, economic, and psychosocial data of patients were collected. Depression was assessed by the Beck Depression Inventory. Health-related quality of life was measured by the Medical Outcomes Study Short-Form 36. Multivariable linear regression analyses were performed. Eight hundred sixty-one patients (373 males, mean age 59.4 +/- 13.2 years) completed the study. Higher monthly income was positively associated with role emotional and mental health (P < 0.05), and so was increased frequency of social activities with social functioning (P < 0.05). The more worries, the stronger the inverse associations with social functioning (P < 0.05) and mental health (P < 0.01). Higher depression scores were associated with lower scores of all Short-Form 36 dimensions (P < 0.01). Higher monthly income and increased social activities are associated with better health-related quality of life, whereas more worries and higher depression scores are associated with worse health-related quality of life of hemodialysis patients.