The invention belongs to the technical field of intelligent polymer materials, and relates to quadruple stimulation response polyamino acid nano-gel and a preparation method and application thereof. According to the method, vinyl amino acid functional monomers are utilized, and the nano-gel is prepared by means of a water-phase controllable free radical polymerization method in the presence of a macro-molecular chain transfer agent and an initiator. According to the method, a polymerization-induced self-assembly method is adopted for preparation of the nano-gel, and a micro-molecular surfactant or an organic solvent is not used in the nano-gel preparing and drug loading process; the obtained nano-gel has good biocompatibility and chirality, the outside temperature and pH are reduced, the particle size after introduction of CO2 gas is increased, the nano-gel is dissolved into water-soluble macro-molecules after a reducing agent is added, and therefore the nano-gel can be used for controlling intelligent release of load molecules.