Combining　surface　imprinting　with　nanomaterials　is　an　effective　solution　to　overcome　template　removal　and　achieve　large　binding　capacity.　In　this　work,　highly　monodisperse　and　uniform-sized　silica　nanoparticles　(NPs)　with　average　diameter　of　∼400　nm　were　synthesized　by　using　tetraethoxysilane　(TEOS)　as　a　single　precursor,　and　then　vinyl　groups　were　introduced　onto　the　surface　of　silica　NPs　by　chemical　modification　of　γ-　methacryloxypropyltrimethoxysilane　(γ-MAPS).　Subsequently,　the　molecularly　imprinted　polymer　(MIP)　coating　was　copolymerized　and　anchored　onto　the　surface　of　vinyl　modified　silica　NPs　dispersed　in　aqueous　media　with　lysozyme　(Lyz)　as　a　template.　The　morphology　and　structure　property　of　the　resultant　MIP-coated　silica　NPs　were　characterized　by　scanning　electronic　microscopy　(SEM),　transmission　electronic　microscopy　(TEM)　and　Fourier　transform　infrared　spectroscopy　(FT-IR).　The　polymerization　and　adsorption　conditions　were　investigated　in　detail　in　order　to　obtain　the　highest　selectivity　and　binding　capacity.　Under　the　optimized　conditions,　the　imprinted　nanoparticles　showed　higher　binding　affinity　toward　the　template　than　non-imprinted　(NIP)　nanoparticles,　and　the　corresponding　imprinted　factor　(a)　reached　1.68.　The　specificity　for　Lyz　recognition　was　evaluated　with　competitive　experiments,　indicating　the　imprinted　nanoparticles　have　a　higher　selectivity　for　the　template.　The　resultant　Lyz-MIP　silica　NPs　could　not　only　selectively　extract　a　target　protein　from　mixed　proteins,　but　also　specifically　enrich　Lyz　from　human　serum.　In　addition,　the　stability　and　regeneration　were　also　investigated,　which　indicated　the　imprinted　silica　NPs　had　excellent　reusability.　©　2012　The　Royal　Society　of　Chemistry.