: Hemodialysis therapy will change the rhythm of a person's life for a long time. It can cause depression which is characterized by changes in behavior such as rejection, anger, fear, feelings of helplessness, hopelessness, anxiety and even suicide. If depression is not handled immediately, it will worsen the quality of life of hemodialysis patients. The purpose of this study was to examine the correlation and differences between the level of depression and the quality of life of hemodialysis patients. The study employed the descriptive comparation and correlation with cross sectional approach. The study was conducted on hemodialysis patients at Public Regional Hospital of Wates Kulon Progo, Yogyakarta, Indonesia. The sampling technique used total sampling. The number of samples in this study were 64 respondents. The research instruments were the Beck’s Depression Inventory (BDI) and QoL-SF36 questionnaire. The analysis test used the Mann Whitney difference test and the contingency coefficient correlation test. The results of the study showed that the majority of hemodialysis patients were 45-54 years (32.8%), male sex (57.8%), with education background of elementary & junior high school (51.6%), married (90.6%), unemployment (28.1%), not depressed (45.3%), and with a moderate quality of life (67.2%). There was a significant difference (p = 0.023), and there was a correlation between depression and quality of life (0.008). It is expected that nurses work together with patients' families to increase patient’s acceptance to the disease, as well as measure depression levels and quality of life regularly.