Detection　of　harmful　chemical　reagents　and　pollutants　is　of　great　significance　for　protecting　human　health　and　environmental　sustainability.　In　this　work,　a　3D　metal-organic　framework,　named　In-BTDI,　has　been　synthesized,　featuring　a　two-fold　interpenetrated　framework.　In-BTDI　shows　intense　luminescence　with　the　emission　peak　at　502　nm　and　exhibits　high　structural　and　photo-stability　in　water　and　common　organic　solvents,　which　provides　a　good　foundation　to　be　unitized　as　a　chemical　sensor.　In-BTDI　can　selectively　and　sensitively　sense　4-nitroaniline　(4-NA)　and　antibiotics　by　the　fluorescence　quenching　effect　not　only　in　the　organic　solvent　but　also　in　water.　It　is　noteworthy　that　the　limits　of　detection　(LOD)　of　4-NA　and　antibiotics　in　water　are　240　and　202　ppb,　respectively,　both　reaching　a　ppb　level,　suggesting　the　good　detection　ability　of　trace　analytes　in　water.　The　sensing　mechanism　was　then　discussed　in　detail.　©　2023　American　Chemical　Society.