Hepatitis C virus (HCV) cell entry is a multistep process mediated by various receptors. Among these receptors, the scavenger receptor class B type Ⅰ (SR-BⅠ) is the one considered to be the first to interact with HCV. SR-BⅠ can bind to HCV envelope glycoprotein E2, in which the hypervariable region 1 (HVR1) segment locating at the N-terminus of E2 protein plays a critical role. The interaction of SR-BⅠ with HCV can not only mediate HCV cell entry, but also attenuate neutralization activity of antibodies against E2 protein, contributing to the HCV immune evasion. Therefore, studying the mechanism of HCV/SR-BⅠinteraction during cell entry can help to identify important targets in the initial step of viral infection, contributing to prevention and treatment of HCV infection. This paper reviews the current knowledge on the biological characteristics of SR-BⅠ and mechanisms of HCV cell entry mediated by virus/SR-BⅠinteraction.