BACKGROUND: In hemodialysis (HD) patients, traditional risk factors cannot explain all of the mortality and morbidity. This study was designed to investigate the effect of depression and health-related quality of life (HRQOL) on prognosis in maintenance HD patients. METHODS: In February 2008, the Beck's Depression Inventory and the Kidney Dialysis Quality of Life-Short Form were utilized to measure depression and HRQOL. Until February 2011, the mortality, cardiovascular events, infection, and hospitalization were investigated, retrospectively. RESULTS: Among the 166 patients, the 3-year cumulative survival rate was 88.8%, and the depression did not affect survival (depression vs. nondepression: 91.8% vs. 87.2%, P=0.437). The upper tertiles in physical component summary (PCS) were correlated with lower mortality (OR, 0.12; P=0.05) and fewer cardiovascular events (OR, 0.09; P=0.024) than the lower tertiles. The upper tertiles in kidney disease component summary (KDCS) were associated with less hospitalization than the lower tertiles (OR, 0.38; P=0.024). After adjusting for multiple variables including age, comorbidity index, and albumin, upper tertiles in PCS were correlated with fewer cardiovascular events than the lower tertiles (OR, 0.08; P=0.038). CONCLUSION: The cross-sectional survey of whether HD patients had depression was not significantly associated with mortality and morbidity. HRQOL was correlated with mortality, cardiovascular events and hospitalization.