Hepatitis C virus (HCV) protease is an enzyme, either viral or cellular, that catalyzes the hydrolysis of the long polyprotein precursor (approximately 3000 amino acids) encoded by HCV genome into at least ten individual proteins, including four structural proteins (C, E1, E2 and p7) and six nonstructural (NS) proteins (NS2, NS3, NS4A, NS4B, NS5A and NS5B). The commonly studied HCV proteases are two virally encode proteases involved in the viral replication of HCV, including HCV NS2/3 protease, a highly hydrophobic protease responsible for the cleavage of NS2 and NS3, and HCV NS3-4A serine protease, a covalent heterodimer responsible for cleavage at four sites of the HCV polyprotein.