Hepatitis C virus (HCV) infection may deteriorate quality of life. The relationship between HCV infection and quality of life in hemodialysis (HD) patients is unknown. The demographic characteristics, comorbidities, biochemical parameters, and Malnutrition-Inflammation Score (MIS) were recorded. Child-Pugh classification, Beck Depression Inventory, and SF-36 were performed. Liver histopathology was examined. Thirty-two patients (21 Child-Pugh-A, 11 Child-Pugh-B) were included. There was high-grade portal necroinflammatory activity in 14, high-grade lobular necroinflammatory activity in 26, and hepatic fibrosis in 19 patients. Three patients had cirrhosis. Patients with a high stage of liver fibrosis had lower social functioning scores than patient with a low stage of fibrosis (P= 0.011). The only correlation was between aspartate aminotransferase and the physical function subscale (r= -0.395, P= 0.025). None of the SF-36 scores differed between Child-Pugh A and B patients. Instead, most of the SF-36 subscale and summary scores were related with hemoglobin, albumin, MIS and Beck Depression Score. Quality of life in HCV-infected HD patients was independent of liver disease severity anchors, but was correlated with anemia, malnutrition, and depression.