Monoclonal antibodies are attractive therapeutic agents in a wide range of human disorders that bind specifically to their target through their complementary-determining regions (CDRs). Small proteins with structurally preserved CDRs are promising alternatives to antibodies. In this study, we presented new antibody mimetics against colorectal cancer marker epidermal growth factor receptor (EGFR) created by CDRs grafting technique. Ten potential graft acceptor sites that efficiently immobilise the grafted CDR loops were selected from three small protein scaffolds by computational identification. The three most involved CDR loops in antibody-receptor interactions extracted from panitumumab monoclonal antibody against domain III of EGFR (EGFR DIII) crystal structure were then grafted to the selected scaffolds through the loop randomization technique. The combination of three CDR loops and 10 grafting sites revealed that three of the 36 combinations showed specific binding to EGFR DIII by binding energy calculation. Thus, the present strategy and selected small protein scaffolds are promising in designing new binders against EGFR with high binding energy.