The invention discloses an amphiphilic core-shell porous polymer microsphere and a preparation method thereof. The preparation method of the amphiphilic core-shell porous polymer microsphere comprisesthe following steps of (1) emulsifying an organic solvent, a surfactant and water, so as to obtain an emulsion; adding into a polystyrene microsphere water solution, and stirring; (b) adding a hydrophobic monomer, a hydrophilic monomer and an initiator into a surfactant water solution, and emulsifying; (c) adding the obtained emulsion in step (b) into the obtained solution in step (a), and stirring; (d) leading nitrogen into the obtained emulsion in step (c), and polymerizing; (e) repeatedly washing by ethyl alcohol and deionized water, and freeze-drying, so as to obtain the amphiphilic core-shell porous polymer microsphere. The amphiphilic core-shell porous polymer microsphere has the advantages that the polystyrene microsphere is used as the basic building unit; by leading the hydrophobic monomer/hydrophilic monomer, the controllable synthesis of the amphiphilic core-shell porous polymer microsphere is realized; the amphiphilic core-shell porous polymer microsphere can be applied tothe fields of medicine release, tissue engineering, biological molecule separation, adsorption, sensing and the like.