The　visible-light-driven　organic　transformation　using　two-dimensional　covalent　organic　frameworks　(2D-COFs)　as　metal-free　heterogeneous　photocatalysts　is　a　green　and　sustainable　approach,　and　it　has　gained　a　surge　of　interest　by　virtue　of　the　photosensitizer＇s　high　crystallinity,　abundant　porosity,　outstanding　stability,　excellent　light-harvesting　ability　and　tunable　structure.　However,　the　guiding　principle　for　designing,　constructing　and　selecting　COF-based　photocatalysts　has　not　been　put　forward　so　far.　Herein,　we　contribute　a　fascinating　strategy　to　guide　the　acquisition　of　excellent　framework　photocatalysts,　which　is　to　screen　them　from　a　series　of　isomorphic　COFs.　As　a　proof　of　concept,　three　new　isomorphic　pyrene-based　2D-COFs　(COF-JLU23,　COF-JLU24　and　COF-JLU25)　with　variable　linkers　were　successfully　synthesized.　In　addition　to　having　similar　crystallinity　and　porosity　with　the　same　pore　size　and　shape,　their　absorption,　emission,　bandgap,　energy　level,　transient　photocurrent　response　and　photocatalytic　activity　could　be　easily　adjustedviaconfiguring　different　linkers　in　frameworks.　Indeed,　COF-JLU24　with　electron　donor-acceptor　characteristics　exhibited　the　best　photocatalytic　activity　among　the　three　isomorphic　COFs　for　C-3　functionalization　reactions　of　indoles,　even　better　than　that　of　the　metal-free　photocatalyst　g-C3N4.　More　importantly,　the　screened　COF-JLU24　as　a　metal-free　photocatalyst　still　displayed　extensive　substrate　adaptability　and　excellent　recyclability.　We　anticipate　that　this　strategy　will　become　a　robust　rule　of　thumb　for　fast　access　to　COF-based　photocatalysts.　In　addition,　we　still　highlight　that　the　present　study　broadens　the　applied　frontier　of　COF-based　photocatalysts.　©　The　Royal　Society　of　Chemistry　2020.