A novel type of smart polymersomes with rapid K(+)-triggered drug-release properties is developed in this work. Block copolymers with biocompatible poly(ethylene glycol) (PEG) as the hydrophilic block and poly(N-isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (PNB) copolymer as the K(+)-responsive block are successfully synthesized. Because of the presence of 18-crown-6 units, the PEG-b-PNB block copolymers exhibit excellent K(+)-dependent phase-transition behaviors, which show a hydrophilic-hydrophobic state in simulated extracellular fluid and present a hydrophilic-hydrophilic state in simulated intracellular fluid. Polymersomes with regular spherical shape and good monodispersity are prepared by the self-assembly of the PEG-b-PNB block copolymers. Both hydrophilic fluorescein isothiocyanate-dextran and hydrophobic doxorubicin are selected as model drugs and are successfully encapsulated into the PEG-b-PNB polymersomes. After being placed in a simulated intracellular fluid with high K(+) concentration, the PEG-b-PNB polymersomes immediately disassemble accompanied by the rapid and complete release of drugs. Such K(+)-responsive polymersomes with the desired drug-release properties provide a novel strategy for advanced intracellular drug delivery and release, which can enhance the safety and efficacy of cancer therapy.