Hypochorous acid plays important roles in numerous physiological and pathological processes. At the cell organelle level, an abnormal concentration of hypochorous acid in the lysosomes causes redox imbalance and the loss of function of the lysosomes. Herein, the first small molecule based, lysosomal-targeted ratiometric fluorescent HOCl probe (Lyso-HA) was synthesized through a rational design. The new probe was highly selective toward HOCl over other reactive oxygen species and exhibits a large variation (up to 97-fold) in its fluorescence ratio (I585/I450), with good signal resolution. The probe Lyso-HA is membrane-permeable and is suitable for ratiometric visualization of exogenous and endogenous HOCl at lysosomes in living cells.