Hepatitis C virus (HCV) is of major social, medical and economic importance. The prevalence of HCV is approximatively 1 % in most developed countries, and much higher in developing countries. HCV infection is the second major cause, after hepatitis B virus infection, for the generation of chronic liver disease and hepatocellular carcinoma. To date, the only reliable model for the study of HCV infection is the chimpanzee. Indeed, there is no robust in vitro infection system, yet. There is thus an urgent need for such an in vitro infection system in order to evaluate therapeutic agents. Here, a process is provided for infecting hepatocyte cell lines with hepatitis C virus in vitro. It is strongly suggested that cell-bound lipoproteins are playing a crucial role during the infection process. In order to obtain a robust infection, the cell-bound lipoproteins have first to be removed from their cellular receptor prior to the addition of viral inocula originating from human sera, the latter being made originally of a virus-lipoprotein complex.