Mimicking noncovalent interaction based processes in nature hag been an important goal of supramolecular chemistry. Here, we report on amphiphilic polypeptides that self-assemble to form nanoscale supramolecular assemblies and are programmed to disassemble in response to a specific protein. Benzenesulfonamide and carbonic anhydrase have been chosen as the ligand and protein, respectively, to demonstrate this possibility. Slice the amphiphilic nanoassembly sequesters hydrophobic guest molecules, the protein-specific disassembly event provides a protein-sensitive molecular release as well We envision that the binding induced disassembly and guest release might open up new opportunities for the next generation of supramolecular assemblies for protein-specific delivery and diagnostics.