Hypochlorous acid (HClO) is a promising diagnostic marker for inflammation and relevant diseases. Although many probes were previously developed for HClO imaging, the development of organ targeting probes is still lacking. Herein, we designed and synthesized a series of cyanine derivatives as ratiometric fluorescent probes to detect endogenous HClO in the lungs with inflammation. By installing diverse lipid chains and amino groups on cyanine, we identified that ClO1, with one n-octadecane chain and two 2-[[2-(dimethylamino)ethyl]methylamino]-ethyl groups, is a superior probe to target the lungs over other major organs in mice. ClO1 was able to sense both exogenous and endogenous HClO in A549 (human lung epithelial) cells through fluorescence ratiometric imaging. In a lipopolysaccharide (LPS)-induced lung inflammation mouse model, ClO1 effectively captured endogenous HClO in the lungs after intravenous administration. Overall, these cyanine-derived probes merit further development as organ targeting HClO sensors.