The present invention discloses a polypeptide that specifically binds beta-catenin. The polypeptide is a TRIB3 mutant having TRIB3 activity after an amino acid sequence is subjected to substitution, deletion, or addition of one or several amino acids. The present invention also discloses a derivative of the polypeptide and the derivative is a chimeric peptide formed by linking the polypeptide to atransmembrane peptide. The present invention discloses an antitumor pharmaceutical composition containing the polypeptide or the polypeptide derivative as an active ingredient and discloses applications of the polypeptide, polypeptide derivative and pharmaceutical composition in preparations of medicines for preventing and/or treating diseases related to TRIB3 and beta-catenin, especially tumors.The pharmaceutical composition has ability of specifically binding to the beta-catenin and blocking binding of TRIB3 and beta-catenin protein, and can reduce protein level of the TRIB3 at the same time. The prepared medicine has advantages of remarkable curative effects, less toxic and side effects, and safe use.