Sulfur dioxide (SO2) plays significant roles in regulating cell apotosis and inflammation. However, there are complex interactions between small biomolecules in cells, and the identification of these coexisting biomarkers remains a challenge. Herein, we report an AND logic gate based fluorescent probe (NY-Lyso), operating by responding to pH differences between organelles in cell and selectively reacting with bisulfite (HSO3-). This approach allows the fluorescence of the probe to remain silent under neutral or alkaline conditions, notably, is activated by costimulation of lower pH and bisulfite. Furthermore, it was confirmed to be biocompatible and could be employed to monitor HSO3- in lysosomes of living cells. The proposed method demonstrated more practical and outstanding capabilities in targeted and real-time monitoring, providing an effective optical tool for biomarker sensing.