Objectives: The LDL receptor (LDL-R) has been proposed as the viral receptor for Hepatitis C virus (HCV). This hypothesis has been based exclusively on in vitro studies. In human mononuclear cells, LDL-receptor gene expression has been demonstrated to parallel and be coordinately regulated to gene expression in the human liver. The purpose of the current study was to determine the mononuclear cell surface expression of the LDL receptor in patients with HCV chronic infection according to viral load. Methods: sixty-eight consecutive untreated chronic hepatitis C patients were studied to determine the mononuclear cell surface expression of the LDL receptor. LDL-receptors were quantified at the surface of mononuclear cells in fresh blood samples taken after fasting using flow cytometry. Results: LDL-receptor expression was significantly associated with LDL-cholesterol (r=-0.25; p=0.03) and HCV-viral load (r= 0.37, p= 0.002). In multivariate analysis, the LDL-receptor expression was significantly associated with HCV viral load, whereas genotype, age , BMI and fibrosis were not. In conclusion, our data provided by a human study, suggest that the LDL receptor may be one of the receptors implicated in HCV replication