Precise detection of inflammatory microenvironment-related viscosity and hypochlorous acid (HClO) contributes to illuminating the pathogenesis and further diagnosing of atherosclerosis (AS). Herein, a dual-lock-controlled mitochondria-targeted fluorescence probe (NS) for simultaneous imaging of HClO and viscosity in AS-related foam cells is presented. NS performs linear increase in green-fluorescence along with increased viscosity (excited at 425 nm), permitting “off–on” fluorescence imaging of viscosity. Meanwhile, upon HClO activation, NS exhibits red-shifted and enhanced fluorescence in orange, thus leading to ratiometric fluorescence quantification of HClO (excited at 465 nm). Such dual-lock-controlled effect makes NS realize simultaneous imaging of viscosity and HClO with high sensitivity and selectivity via “off–on” and ratiometric fluorescence readouts, respectively. Besides, endowed with mitochondria-targeting capacity, NS achieves in situ imaging of mitochondria viscosity and HClO in living RAW264.7 cells. Importantly, for the first time, NS realizes simultaneous imaging of mitochondria viscosity and HClO in macrophage-derived foam cells, revealing the close association between HClO level and viscosity change in mitochondria during foaming translation of macrophages in atherogenesis. This work not only provides a novel strategy and tool to image organelle-located viscosity and HClO in living systems, but also holds great potential in early diagnosis of AS.