The invention relates to a preparation method of a hollow mesoporous silica nanoparticle. The preparation method comprises the following steps: obtaining a polymer-silica composite nanoparticle having a core-shell structure by adopting spherical aggregations of an amphiphilic segmented copolymer in an aqueous solution and a cationic surfactant hexadecyl trimethyl ammonium bromide as double templates and ethyl orthosilicate as a silicon source and by hydrolyzing the silicon source under an alkaline condition; and calcining to remove the templates to obtain the hollow mesoporous silica nanoparticle. The preparation method has the advantages of simplicity, mild reaction condition, and cheap experiment raw materials, and the prepared mesoporous silica nanoparticle has the advantages of high specific surface area, high pore volume, and good biological compatibility. The hollow structure enables the drug loading amount to be substantially improved, nanometer gold, nanometer silver, magnetic iron oxide particles, quantum dots, a contrast agent and the like to be loaded, so the hollow mesoporous silica nanoparticle can be used as a targeting drug release carrier, can be used for magnetic resonance image analysis, and has good application prospects in the fields of the diagnosis and the treatment of cancers.