摘要： Highly reliable detection, imaging, and monitoring of reactive oxygen species (ROS) at subcellular organelles are critical for understanding the biological roles of ROS and learning the pathogenesis of some diseases. In this study, we presented an interference-free surface-enhanced Raman scattering (SERS)-active nanoprobe for the intracellular ROS detection. This nanoprobe was designed as an Au core-Ag shell nanoparticle (Au@Ag NPs) with a SERS reporter (4-mercaptobenzonitrile) resided in the inner of the core-shell. Intracellular ROS is able to etch the Ag shell and dramatically decreases the SERS intensity of the SERS reporters. It is worth mentioning that the Raman band of the reporter we used in this study locate in the cellular Raman-silent region (1800?2800 cm?1), which eliminates interference possibility from cellular molecules. The shell can also further protect the reporters from the interference of mediums. We detected ROS at subcellular organelle level, e.g. mitochondria, by modifying the surface of the nanoprobes with a mitochondria-targeting peptide. And for the first time, the SERS-based monitoring of ROS at mitochondria during the photothermal therapy process was validated and the profiles of the ROS distribution were disclosed by SERS mapping.