The invention discloses a preparation method of a targeted nano vaccine based on a metal-polyphenol network structure. The preparation method comprises the following steps that mesoporous silica nanoparticles loaded with ovalbumin OVA are prepared, mannose-modified tannic acid molecules are synthesized, and the surfaces of the mesoporous silica nanoparticles loaded with the ovalbumin OVA are coated with metal-polyphenol network coatings, so that the mesoporous silica nanoparticles loaded with the OVA and with the surfaces coated with the metal-polyphenol network coatings are obtained, therefore the targeted nano-vaccine based on the metal-polyphenol network structures is obtained, and the targeted nano-vaccine is named as MS@OVA@MPN@Man. According to the preparation method, the surfaces are coated with the metal-polyphenol network coatings, so that leakage of OVA is prevented, and the lysosome escape function of the nanoparticles is increased; and meanwhile, mannose is modified on thesurface to target a mannose receptor on the surface of an immune cell, so that the uptake capacity of the cell to the mannose receptor is enhanced to improve the vaccine delivery efficiency, and the problems of targeting of the nano vaccine and lysosome escape efficiency are solved.