An inhibitor-resistant HCV NS3 protease is provided which is useful to screen for compounds having therapeutic value against drug resistant HCV strains. In particular, the inhibitor-resistant HCV NS3 protease comprises an amino acid sequence which is mutated in the substrate binding pocket thereof rendering the protease resistant to inhibitor. In a specific aspect of the present invention, at least one of the amino acids at position 155, 156 and 168 of the HCV NS3 protease is mutated to yield an inhibitor-resistant protease.