Benzophenone　derivatives　(BPs),　as　synthetic　chemicals　widely　used　in　personal　care　products,　have　drawn　increasing　attention　due　to　their　potential　health　risks.　However,　monitoring　BPs　in　biological　samples　remains　challenging　due　to　their　complex　matrices　and　the　deficiency　in　sensitivity　and　selectivity　in　current　methods.　Herein,　a　method　combining　hierarchically　flower-like　hollow　covalent　organic　frameworks　(HFH-COFs)　with　high-performance　liquid　chromatography-tandem　mass　spectrometry　(HPLC-MS/MS)　was　established　for　the　enrichment　and　detection　of　BPs　in　serum　samples.　The　HFH-COFs　were　synthesized　at　room　temperature　and　employed　as　an　adsorbent　due　to　their　advantageous　properties.　The　as-prepared　HFH-COFs　exhibited　high　specific　surface　area　(2286.53　m(2)/g),　excellent　chemical　stability,　and　good　thermal　stability,　making　them　ideal　for　efficient　enrichment　applications.　Under　optimized　experimental　conditions,　five　BPs　were　effectively　enriched　and　quantified　by　HPLC-MS/MS　in　the　range　of　50.0-5000.0　ng/L　with　good　linearity　(r　＞　0.9992).　The　limit　of　detections　was　0.5-10.0　ng/L.　Furthermore,　HFH-COFs　showed　high　enrichment　factors　even　over　multiple　adsorption-desorption　cycles.　This　study　proposed　a　reliable　and　efficient　method　for　monitoring　endocrine-disrupting　compounds　in　complex　biological　samples　and　highlighted　the　potential　of　HFH-COFs　as　a　superior　adsorbent　material　for　BP.