Abstract: The present disclosure provides a pH-sensitive membranolytic polymer material and a preparation method and application thereof. The pH-sensitive membranolytic polymer material has the structure shown in Formula (I). At normal physiological pH, the polymer material is hydrophobic neutral, and can be self-assembled into PEG coated nanoparticles with weak interaction with cell membrane; when the pH decreases, the polymer material can be protonated to form an amphiphilic structure consisting of hydrophobic domain and cationic domain, which has strong interaction with the cell membrane and strong membranolytic activity, so the polymer material can kill tumor cells or bacteria efficiently and selectively.