The invention provides a fluorescent probe for selectively responding to H2S based on BODIPY fluorescent dye targeting lysosome, and preparation and application of the probe. The probe selects BODIPY dye as a fluorophore and 2, 4-dinitrobenzenesulfonyl as a recognition group. A sensing mechanism is based on H2S to induce cracking of 2, 4-dinitrobenzenesulfonyl in the probe, so that a photoinduced electron transfer (PET) process is inhibited. The probe detects H2S through ultraviolet and fluorescence spectrometers and is not interfered by other amino acids, active sulfides, representative anions and the like, the detection process is simple, convenient, rapid and sensitive, and the detection limit is 4.75 nM. More importantly, the probe can target lysosome and detect H2S in cells at the same time, and has a good application prospect in the field of biological monitoring.