Malignant tumors are one of the main causes for human death and are tightly associated with overexpression of reactive oxygen species (ROS) in pathological processes. Therefore, in vivo monitoring of ROS, especially ONOO-, remains of great significance for diagnosis and therapy of tumors to improve the survival rate. Herein, we designed and constructed a reliable near-infrared (NIR) ratiometric fluorescent biosensor CDMS for monitoring the fluctuations of ONOO- in the process of tumor progression. CDMS featured outstanding stability to photoirradiation, substantial quantum yields, rapid response (<5 s), high selectivity and excellent biocompatibility. Moreover, CDMS exhibited distinct ratiometric fluorescence signal changes after reacting with ONOO-. Fluorescence imaging in immune stimulated cells indicated that CDMS was competent to determine the levels of ONOO- in the cellular level. Remarkably, CDMS was further applied in monitoring the expression of ONOO- in a peritonitis mouse model and tumor-bearing mouse model. Based on the excellent properties of CDMS, the probe exhibited the potential for noninvasive in vivo visualization of ONOO- in the occurrence and process of tumor development. It is envisioned that CDMS can be employed as a promising tool for monitoring the ONOO- fluxes in tumor pathological progression, especially for tumor diagnosis and therapy.