Provided are a polypeptide specifically binding to TRB3 and application thereof in preparation of drugs for treating and/preventing pulmonary fibrosis. The amino acid sequence of the polypeptide is represented by SEQ ID No. 12 in a sequence list, or two or more amino acids in the amino acid sequence as represented by SEQ ID No. 12 in the sequence list are replaced with unnatural amino acids having side chains that can be linked to each other. The polypeptide and derivatives thereof can specifically bind to TRB3, thereby blocking the interaction between TRB3 and MDM2 proteins.