Effective and cancer diagnosis is expected to ease the burden of continued increased deaths worldwide. Herein, we proposed viscosity of the tumor microenvironment as a biomarker and further develop a versatile optical agent, for monitoring tumor microenvironmental viscosity alterations to achieve cancer diagnosis, therapeutic effect tracking, and anticancer drug screening. When in highly viscous media, near-infrared signals of are specifically activated, endowing the probe with the capacity of avoiding biological autofluorescence and achieving high signal-to-noise ratio imaging. The results of vascular imaging disclosed higher fluorescence of the blood vessels in the tumor than the normal ones, implying tumors being pointed out with brighter fluorescence. With the assistance of fluorescence imaging technology, achieved identifying cancer with high signal-to-noise ratio imaging. In addition, the capability of to evaluate anticancer drug efficacy with viscosity as a robust biomarker was explored. Furthermore, as a proof of concept, screening of the anticancer drugs is also realized through monitoring of the microenvironmental viscosity fluctuations of the tumor with . Note that this proposed fluorescence imaging method outperforms the clinical hematoxylin and eosin (H&E) staining assay with the advantageous features of and characteristics. We expected that this unique strategy will reinvigorate the continued perfection of the cancer diagnosis systems.