The invention discloses a polypeptide specifically combined with beta-catenin protein with high affinity, and application and a synthesis method of the polypeptide. The amino acid sequence of the polypeptide is LEHRERSLQT(X1)RDIQRML(X2)P, wherein X1 is leucine, norleucine or homoleucine, and X2 is phenylalanine, 1-naphthyl alanine, 2-naphthyl alanine, 2-anthryl alanine or 9-anthryl alanine. The polypeptide is used for inhibiting growth of cancer cells. By the polypeptide, various tumor treatment targets can be achieved. The polypeptide inhibits opening of a beta-catenin protein-mediated Wnt signal pathway by inhibiting mutual combination of the beta-catenin protein and BCL9 in the cancer cells, so that growth of tumors is inhibited, self-apoptosis of the cells is induced, and the tumor disease treatment targets are achieved. The synthesis method of the polypeptide is simple and easy to implement, and the final product has high yield efficiency, has mass production potential, and has great drug clinical transformation potential.