Cell　membrane-targeted　bioimaging　is　a　prerequisite　for　studying　the　roles　of　membrane-associated　biomolecules　in　various　physiological　and　pathological　processes.　However,　long-term　in　situ　bioimaging　on　the　cell　membrane　with　conventional　fluorescent　probes　leads　to　diffusion　into　cells　from　the　membrane　surface.　Therefore,　we　herein　proposed　a　de　novo　strategy　to　construct　an　antidiffusion　probe　by　integrating　a　fluorochrome　characterized　by　strong　hydrophobicity　and　low　lipophilicity,　with　an　enzyme　substrate　to　meet　this　challenge.　This　precipitating　fluorochrome　HYPQ　was　designed　by　conjugating　the　traditionally　strong　hydrophobic　solid-state　fluorochrome　6-chloro-2-(2-hydroxyphenyl)　quinazolin-4(3H)-one　(HPQ)　with　a　2-(2-methyl-4H-chromen-4-ylidene)　malononitrile　group　to　obtain　closer　stacking　to　lower　lipophilicity　and　elongate　emission　to　the　far-red　to　near-　infrared　wavelength.　As　proof-of-　concept,　the　membrane-associated　enzyme　gamma-glutamyltranspeptidase　(GGT)　was　selected　as　a　model　enzyme　to　design　the　antidiffusion　probe　HYPQG.　Then,　benefiting　from　the　precipitating　and　stable　signal　properties　of　HYPQ,　in　situ　imaging　of　GGT　on　the　membrane　was　successfully　realized.　Moreover,　after　HYPQG　was　activated　by　GGT,　the　fluorescence　signal　on　the　cell　membrane　remained　unchanged,　with　incubation　time　even　extending　to　6　h,　which　is　significant　for　in　situ　monitoring　of　enzymatic　activity.　In　vivo　testing　subsequently　showed　that　the　tumor　region　could　be　accurately　defined　by　this　probe　after　long-term　in　situ　imaging　of　tumor-bearing　mice.　The　excellent　performance　of　HYPQ　indicates　that　it　may　be　an　ideal　alternative　for　constructing　universal　antidiffusion　fluorescent　probes,　potentially　providing　an　efficient　tool　for　accurate　imaging-　guided　surgery　in　the　future.