Current proteomics research on drug mechanisms primarily focuses on whole-cell studies, which are inadequate for effectively analyzing the dynamic molecular networks and mechanisms between organelles. This study, utilizing organelle proteomics analysis after treating cells with 30 different clinical drugs, uncovering different durgs induced quiet different changes in organelle protein abundance. It also reveals extensive protein translocation between organelles, a phenomenon that is nearly undetectable at the whole-cell level. Additionally, the study highlights significant differences in the interaction relationships of the same protein complexes within different organelles.