Background: Many people on dialysis suffer a variety of conditions that can affect frailty (the condition or quality of being frail), such as comorbidities, disabilities, dependence, malnutrition, cognitive impairment and poor social conditions. Frailty is suspected to affect quality of life (QoL). Objectives: The study aimed to evaluate the effect of the different components of frailty on the QoL of people on dialysis. Methods: We enrolled 203 out of 233 prevalent patients on dialysis in the Trieste area of Italy. We applied the Short-Form 36 (SF-36) questionnaire, Activities of Daily Living, Instrumental Activities of Daily Living, Subjective Global Assessment scales and Karnofsky Index. In addition we analysed their social conditions. Results: Dependence, malnutrition and disability had a negative role on QoL. Living with family and good social-economic conditions were significantly related to a better QoL. Conclusions: Dependence, malnutrition, disability, poor social and economic conditions have a significant effect on life quality. The role of comorbidities appears to be less important. Screening of patients, nutritional and functional rehabilitation and prevention of social isolation appear to be indispensable in guaranteeing a satisfactory life quality.