The invention discloses a preparation method of multi-stimulus synergistic response drug-release bone cement. The method comprises the following steps of firstly, preparing a drug-loading SiO2 layer coated drug-loading magnetic porous polymer microsphere, forming a polyelectrolyte shell layer on the surface of the microsphere, and etching an SiO2 layer to form a drug-loading magnetic response microcapsule; and then coating the surface of the microcapsule with a drug-loading P(NIPAM-AM) / MMT temperature-sensitive layer, coating the surface of the temperature-sensitive layer with a chitosan hydrogel layer, finally uniformly mixing a pH-temperature-magnetic field synergistic response microcapsule, a P(MMA-HEMA) water-swelling microsphere and PMMA bone cement powder with a liquid phase, performing stirring, and performing injection. The bone cement can autonomously and slowly release drugs at the early stage of tumor recurrence; when the tumor is aggravated, the drug release amount can be controlled by applying a magnetic field, and meanwhile, thermal therapy can be performed on the tumor part by combining the magnetic field with the temperature-sensitive layer; and when the magnetic field stops, the drug release is slow, the local pH value returns to normal, and the drugs are no longer released.