Spatiotemporal imaging is of enormous use to explore organelle biology, necessitating organelle-tracing techniques reliable in varied cell stress. We herein reported lysosomal imaging using rhodamine-X-integrated sialic acid (ROXSA), which is stably maintained in lysosomes irrespective of lysosomal pH changes. Exhibiting bright fluorescence and superior photostability, ROXSA enables 120 h continual tracking of fusion/fission of lysosomes and mitochondrion-lysosome interaction in mitophagy. Relative to conventional acidotropic probes prone to dissipation from stressed lysosomes, ROXSA offers a new route for long-term tracking of stressed lysosomes relevant to diverse pathological conditions.