A novel amphiphilic squarylium indocyanine (LysoCy) is reported for remarkable lysosome tracking in live cells. LysoCy performs as a promising lysosome tracker with low cytotoxicity, a strong binding affinity and clear subcellular labelling. The long-term dynamics of lysosomes can be revealed by LysoCy for up to 2 days of culture, while the working duration of commercial dye is no longer than 1 hour. Our work provides a good alternative tool for long-term live cell imaging.