This project employed TMEM192-3×Flag-mediated lysosome immunoprecipitation (Lyso-IP) followed by mass spectrometry to investigate lysosomal proteomes under normoxia and hypoxia/reoxygenation (H/R) stress. Our study focuses on the mechanisms of lysosomal renewal, revealing that damaged lysosomes undergo budding-type fission (B-fission) to produce functional daughter lysosomes. The dataset provides a comprehensive resource for exploring stress-responsive lysosomal proteins and organelle quality control pathways.