Objective: to verify the association between the health-related quality of life of chronic renal patients on hemodialysis with sociodemographic, clinical, depression and medication adherence characteristics. Method: a cross-sectional study with 183 chronic renal patients undergoing hemodialysis in the state of Rio Grande do Sul, Brazil. A sociodemographic and clinical questionnaire, Kidney Disease and Quality of Life Short-Form, Beck Depression Inventory and Morisky Medication Adherence Scale - eight items were used. Among the variables, comorbidities, complications of kidney disease and intercurrences during and after hemodialysis were evaluated. The analysis was performed with descriptive and analytical statistics. Results: 55.2% of the patients were 60 years old or older, 35.0% were hypertensive, with regular quality of life, average of 62.61. Scores below average in the dimensions of quality of life were mainly associated with repetitive infections and edema as complications of the disease, pain during hemodialysis and weakness afterwards. Low drug adherence resulted in a worse quality of life, impacting ten of the 20 dimensions evaluated and depression in all, except for patient satisfaction. Conclusion: reduced quality of life in this population is associated with depressive symptoms, complications such as repetitive infections, pain and anemia, weakness after the dialysis session and low medication adherence. Actions aimed at changing these factors can promote well-being.