The invention discloses a preparation method of pomegranate-shaped organic-inorganic nano-composite microspheres, which comprises the following steps: mixing an aqueous dispersion solution of silicon dioxide modified by proper amount of double-bond silane coupling agent in a coupling method with a phenylpropyl monomer, anionic emulsifier, non-anionic emulsifier and water, and stirring simply, so that a milky emulsified liquid is obtained; adding initiator to perform emulsion polymerization in the presence of silicon dioxide, so that the pomegranate-shaped organic-inorganic nano-composite microspheres with multiple silicon dioxide particles wrapped in phenylpropyl emulsion particles are obtained finally and are stably dispersed in the emulsified liquid. The preparation method has the advantages that the sources of the raw materials are extensive, the raw materials are easy to obtain, the preparation process is simple, and moreover, in the prepared pomegranate-shaped organic-inorganic nano-composite microspheres, the wrapping rate of silicon dioxide is high, the structure is neat and the placement stability is good. The adhesion property and the film forming performance of the composite microsphere particles are adjustable, the adhesive force and the transparency of the corresponding glue film are good, and the organic-inorganic nano-composite microspheres can be applied to the fields of coating, textile, rubber, plastics, biology, medicine and the like.