Hepatitis C virus is considered one of the worldwide viruses with very large percentage of infection in population. It is as an epidemic disease in Egypt. Previously, the introduced compounds (a and b) in this study were investigated and gave good binding affinity and good inhibition activity with wild-type HCV NS3 protease. In the present work, the calculated molecular docking and the binding energy calculations are performed to predict the inhibition activity of suggested compounds against some mutated HCV NS3 proteases. Compound a has hexa-peptide with α-ketoacids instead of the thiol group (SH) of cysteine residues attached to monomer cellulose at position 6 and compound b has hexa-peptide with α-ketoacids instead of the thiol group (SH) of cysteine residues attached to dimer cellulose at position 6. Based on the calculated binding energy and the number of hydrogen bonds in docking interaction between the compounds and mutated NS3 protease, the inhibition activity of compounds a and b with NS3 protease mutations is more than that with wild-type NS3 protease. Especially with D168V NS3 protease mutation. The mutation in virus enzymes is one of the major obstacles in hepatitis C virus treatment.