Background: Hemodialysis improves renal function and increases lifetime. However, it causes a fundamental change in the whole life of patients. Many of these patients express their fears of an unacceptable life. Objectives: This study aimed to evaluate the quality of life and death anxiety among patients on hemodialysis and determine their personality and demographic predictors. Methods: A total of 154 participants were recruited from the hemodialysis units of hospitals in Zahedan, the southeast of Iran. The participants completed the World Health Organization Quality of Life Brief Scale, Revised NEO Personality Inventory, and Templar's Death Anxiety Scale. Results: In this study, 60.4% of the patients had high levels of death anxiety. About 70% of the patients had low or moderate levels of quality of life. Conclusions: Personality is an essential factor in predicting health-related quality of life and death anxiety. This result provides a better understanding of the determinants of death anxiety and HQOL.