Background: Health-related quality of life (QOL) is affected in hemodialysis patients (HD). A number of factors such as age, anemia, and comorbidity had been implicated in decreased QOL. Erectile dysfunction (ED) is a frequent and potentially treatable complication in HD patients. In this cross-sectional study, we aimed to evaluate the possible relation between the QOL and ED in HD patients. Patients and Methods: Among the 511 chronic HD patients dialyzed in 11 outpatient HD centers, 148 male patients (mean age: 46 ± 9 years) were included. The mean time on dialysis was 41 ± 35 months (range: 3–203 months). Biochemical parameters such as BUN, creatinine, hemoglobin, serum albumin and Kt/V were measured. The QOL of the patients were measured with the short form of Medical Outcomes Study (SF-36), physical component scores (PCS) and mental component scores (MCS) were calculated. The ED was evaluated by the International Index of Erectile Function (IIEF). Results: One hundred and four of the 148 patients (70%) had ED. Hemoglobin levels were correlated with PCS (r = 0.197, p = 0.02) and MCS (r = 0.20, p = 0.019). Patients with ED had lower scores in nearly all the components related to PCS and MCS as compared to patients without ED. IIEF score was correlated with PCS (r = 0.369, p < 0.001) and MCS (r = 0.308, p < 0.001). In linear regression analysis, IIEF score and hemoglobin levels were the independent variables that predicted both PCM and MCS. Conclusion: ED, a frequent complication in HD patients, was related to QOL together with anemia. Successful treatment of ED and anemia may lead to improvement in QOL in HD patients.