Perfluoroalkyl　carboxylic　acids　(PFCAs)　are　a　class　of　persistent　organic　pollutants　(POPs),　which　posed　various　hazards　to　organisms,　including　reproductive,　developmental,　neurological,　and　immunological　toxicity.　Consequently,　developing　an　analytical　method　aimed　at　achieving　highly　sensitive　detection　of　trace　amounts　of　PFCAs　in　complex　samples　is　clearly　of　great　significance.　Herein,　the　Fluorine-functionalized　covalent　organic　framework　(F-COF)　was　synthesized　at　ambient　temperature,　which　has　the　advantages　of　high　specific　surface　area　(1297.7　m2　g-1),　suitable　selective　adsorption　pore　size　and　good　stability.　Based　on　the　multiple　effects　of　suitable　pore　size,　fluorine-fluorine　interactions　and　hydrophobic　interactions,　F-COF　exhibited　high　adsorption　performance　towards　PFCAs.　Accordingly,　the　method　of　F-COF-based　dispersive　solid-phase　extraction　(dSPE)　coupled　with　UPLC-MS/MS　was　developed　for　the　quantitative　analysis　of　5　PFCAs　in　complex　biological　samples.　The　results　showed　that　the　good　linearity　for　the　5　PFCAs　within　the　concentration　ranges　of　0.4　to　104　ng　L-1,　with　correlation　coefficients　(r)　all　greater　than　0.9993.　The　enrichment　factors　(EFs)　ranged　from　11.4　to　22.3　folds,　and　the　limits　of　detection　(LODs)　were　0.11　to　0.17　ng　L-1.　The　established　method　provided　a　powerful　tool　for　the　enrichment　and　detection　of　PFCAs　in　mice　serum　and　tissue.　F-COF　holds　promising　application　prospects　as　a　solid-phase　extraction　material　for　efficient　enrichment　separation　and　detection　of　PFCAs.　©　2025　Elsevier　B.V.