Hypochlorous acid (HOCl), as an indispensable signaling molecule in organisms, is one of the key members of reactive oxygen species (ROS). However, in vivo, real-time dynamic near-infrared fluorescence imaging of HOCl levels in the 1400-1700 nm sub-window (NIR-IIb) remains a major challenge due to the lack of suitable detection methods. Herein, a general design of HOCl-responsive NIR-IIb fluorescence nanoprobe is proposed by integrating NaLuFYb/Er@NaLuF downshift nanoparticles (DSNPs) and HOCl recognition/NIR-IIb emissive modulation unit of MS (M = Cu, Co, Pb) nanodots for real-time monitoring of HOCl levels. The fluorescence modulation unit of MS nanodots presents remarkably enhanced absorption than Yb sensitizer at 980 nm and greatly inhibits the NIR-IIb fluorescence emission via competitive absorption mechanism. While, the MS nanodots are easily degraded after triggering by HOCl, resulting in HOCl responsive turn-on (≈ten folds) NIR-IIb emission at 1532 nm. More importantly, in vivo highly precise and specific monitoring of inflammatory with abnormal HOCl expression is successfully achieved. Thus, the explored competitive absorption mediated quenching-activation mechanism provides a new general strategy of designing HOCl-responsive NIR-IIb fluorescence nanoprobe for highly specific and sensitive HOCl detection.