Background: Dialysis patients experience multiple symptoms impairing their quality of life. A relationship seems to exist between the cultural context and the burden of symptoms. In this study, the prevalence and severity of 30 symptoms and their relationship with quality of life among hemodialysis patients in Switzerland is explored. Methods: A cross-sectional correlation design was used with a convenience sample of 119 patients from five dialysis units. Presence and severity of symptoms were assessed with the Dialysis Symptom Index and quality of life with the WHOQOL-Bref questionnaire. Multivariate linear regressions were used to examine the relationship between the prevalence and severity of symptoms, respectively, and quality of life. T-tests and Fisher’s tests were used for the international comparisons. Results: On average, patients reported 10 symptoms and often rated these as “somewhat bothersome”. The most frequent were: lack of energy, dry skin, trouble falling asleep, trouble staying asleep, and muscle cramps. Average symptoms prevalence and severity levels were both observed to decrease patients’ quality of life, items related to physical health and psychological state having the greatest impact. Prevalence and severity of psychological symptoms and prevalence of sex-related symptoms seem to be influenced by patients’ cultural context. Conclusions: These results demonstrate that patients on chronic hemodialysis present several symptoms that affect their quality of life. Healthcare professionals should develop strategies to identify more properly these symptoms, especially sex-related and psychological symptoms.