The invention discloses a preparation method and a use of poly(lactic-co-glycolic acid) (PLGA) microspheres as nucleic acid vaccine vectors. A result of an animal immunization experiment shows that the PLGA microspheres can be utilized as gene vaccine vectors. Principles of the PLGA microspheres comprise that 1, the PLGA microspheres have core-shell structures; surface polymers comprise polymine, PLGA, glucose, chitosan, polylysine, FeCl3 and FeCl2; and through static electricity, dewatering interaction and hydrogen bond-nucleic acid vaccine interaction, a nucleic acid vaccine is concentrated to form a compact nucleic acid vaccine so that nucleic acid vaccine degradation is reduced in vivo; 2, the PLGA microspheres have magnetism and thus after immunization injection, in a strong magnetic field, the distribution of the PLGA microspheres in muscular tissue is improved and the defect of limited contact between the PLGA microspheres and target cells is overcome; and 3, through long-term strong magnetic field induction, a magnetic PLGA microsphere / nucleic acid vaccine complex can enter into the skin; and because of rich antigen presenting cells in the skin, a strong and fast immune response can be induced.