Inducing and monitoring cell apoptosis in a real-timemanner arecrucial for evaluating the therapeutic effect of drugs and avoidingexcessive treatment. Although promising advancements have been madeto monitor cell apoptosis by assessing cell membrane integrity, thechronic compromise of cellular fitness caused by imbalance proteostasisis not visible and hard to be detected. As an indicator for cell apoptosis,imaging of aggregated proteins provides a new direction. Herein, wedesign a peptide-conjugated probe (QRKN) that can induce mitochondrialdysfunction for self-reporting cell apoptosis by imaging aggregatedproteins. Specifically, QRKN can be cleaved into the & alpha;-helix-formingpart (QRK) and azide-modified small-molecule part (N) by overexpressedcathepsin B (CB) in tumor cells. The QRK part can destroy the mitochondrialmembrane and promote cytochrome c (Cyt c) efflux and caspase 3 expression.The other N part can inhibit the activity of mitochondrial complexIV (Mito-IV) and decrease the expression level of adenosine triphosphate(ATP). Two signaling pathways cooperatively induce mitochondrial dysfunction,resulting in protein aggregation and cell apoptosis ultimately. Meanwhile,the cell apoptosis process can be monitored based on QRKN, which ishighly sensitive to the aggregated protein-triggered viscosity change.The self-reporting probe can monitor therapeutic responses and providevaluable diagnosis information.