In　this　work,　core-shell　structured　Ti4+-immobilized　magnetic　covalent　organic　frameworks　(denoted　as　Fe3O4@TAPTDHTA-Ti4+　composites)　were　prepared　for　enhanced　phosphopeptide　enrichment　by　one-pot　synthesis　of　COFs　shell　with　inherent　bifunctional　groups　on　Fe3O4　NPs　and　further　Ti4+　immobilization.　The　widely　distributed　bifunctional　groups　could　provide　abundant　chelating　sites　for　Ti4+　immobilizing.　Combining　with　the　high　specific　surface　area　and　mesoporous　structure,　the　Fe3O4@TAPTDHTA-Ti4+　composites　exhibited　excellent　enrichment　efficiency　for　phosphopeptides,　such　as　low　detection　limit　(0.05　fmol　μL−1),　high　selectivity　(1:5000　of　molar　ratio　of　β-casein/bovine　serum　albumin　(BSA)　tryptic　digests),　high　adsorption　capacity　(62.9　μg　mg−1)　and　strong　size-exclusive　effect　(1:250:250　of　molar　ratio　of　β-casein　tryptic　digest/β-casein/BSA).　In　addition,　this　method　was　general　for　immobilizing　other　metal　ions　(Zr4+　and　Fe3+).　Notably,　the　Fe3O4@TAPTDHTA-Fe3+　composites　exhibited　controllable　affinity　towards　mono-phosphopeptides　and　multi-phosphopeptides.　Furthermore,　the　Fe3O4@TAPTDHTA-Ti4+　composites　were　successfully　applied　to　selectively　capture　phosphopeptides　from　complex　biological　samples　including　the　tryptic　digest　of　nonfat　milk,　human　serum　and　human　saliva.　More　significantly,　3333　phosphopeptides　derived　from　1409　phosphoproteins　with　3492　phosphorylation　sites　were　clearly　identified　from　the　tryptic　digest　of　HeLa　cell　lysate.　In　addition　to　providing　a　potential　excellent　enrichment　probe　for　comprehensive　phosphoproteomic　analysis,　this　study　also　offers　a　new　perspective　for　the　functionalization　of　COFs.　©　2021　Elsevier　B.V.