Currently,　great　challenges　to　top-down　phosphoproteomics　lie　in　the　selective　enrichment　of　intact　phosphoproteins　from　complex　biological　samples.　Herein,　we　developed　a　facile　approach　for　synthesis　of　Ti4+-immobilized　affinity　silica　nanoparticles　and　applied　them　to　the　selective　separation　and　enrichment　of　intact　phosphoproteins　based　upon　the　principle　of　metal(IV)　phosphate/phosphonate　chemistry.　The　as-prepared　affinity　materials　exhibited　high　selectivity　and　adsorption　capacities　for　model　phosphoproteins　(328.9 mg/g　for　β-casein,　280.5 mg/g　for　ovalbumin,　and　225.8 mg/g　for　α-casein),　compared　with　nonphosphoproteins　(79.28 mg/g　for　horseradish　peroxidase,　72.70 mg/g　for　BSA,　and　27.28 mg/g　for　lysozyme).　In　addition,　the　resuability　of　the　affinity　silica　nanoparticles　was　evaluated,　and　the　results　demonstrated　a　less　than　10%　loss　of　adsorption　capacity　after　six　adsorption–regeneration　cycles.　The　practicability　of　the　affinity　materials　was　demonstrated　by　separating　phosphoproteins　from　protein　mixtures　and　drinking　milk　samples,　and　the　satisfactory　results　indicated　its　potential　in　phosphoproteomics　analysis.　©　2017　WILEY-VCH　Verlag　GmbH　&　Co.　KGaA,　Weinheim