Low quality of life, depression and poor quality of sleep are associated with increased mortality in hemodialysis patients. It is not clear which factor has the highest predictive power and what the core element is to explain the predictability. We thus conducted a prospective cohort study that included 151 hemodialysis adults. Three traits of interest were assessed by World Health Organization Quality of Life questionnaire, an abbreviated version (WHOQOL-BREF), Taiwanese Depression Questionnaire, and Athens Insomnia Scale, respectively. They were followed for more than 3 years and the all-cause mortality was 30.5%. The prevalence of quality of life at the lowest tertile, depression and poor quality of sleep was 19.9%, 43.0% and 74.2%, respectively. Discriminant analysis showed the standardized coefficient of each factor as 0.813, -0.289 and 0.066, indicating the highest discriminating power by quality of life to predict mortality. Question 15 "how well are you able to get around?" in the physical health domain of WHOQOL-BREF independently associated a hazard ratio of mortality 0.623 (95% confidence interval 0.423-0.918). Subjective perception of overall quality of life was more related to psycho-social-environmental factors. In conclusion, mobility is an independent and powerful predictor to long term mortality in patients on chronic hemodialysis.