The　morphology　of　nanomaterials　is　one　of　essential　factors　for　their　unique　properties.　Herein,　a　hollow　covalent　organic　framework　with　a　flower-like　structure　(HFH-COF)　was　synthesized　at　room　temperature.　The　synthesized　HFH-COF　has　a　very　large　specific　surface　area,　mesoporous　structure,　excellent　chemical　stability,　and　good　crystallinity.　The　special　morphology　endowed　HFH-COF　with　high　specific　surface　area　utilization　and　rapid　mass　transfer　rate,　resulting　in　faster　equilibration　time　and　better　extraction　performance　than　spherical　COF　(S-COF).　Subsequently,　combined　with　high-performance　liquid　chromatography-tandem　mass　spectrometry　(HPLC-MS/MS),　an　efficient　and　sensitive　method　was　established　for　microcystins　(MCs)　detection.　The　developed　method　has　low　detection　limits　(0.6-0.8　pg　mL−1),　wide　linear　ranges　(1.5-1000.0　pg　mL−1,　R　≥　0.9993),　and　acceptable　reproducibility　(RSD　≤　7.6%,　n　=　6).　Real　biological　samples　were　analyzed　by　the　developed　method,　and　trace　levels　of　MC-YR,　MC-RR　and　MC-LR　were　detected.　The　results　indicate　that　the　synthesized　HFH-COF　is　an　ideal　sorbent　for　efficient　extraction　of　MCs　from　complex　biological　samples.　©　2023　The　Royal　Society　of　Chemistry.