<p>Caspase-1 plays a pivotal role in the initiation and progression of pyroptosis. The accurate in situ detection of intracellular caspase-1 remains challenging due to its low abundance in macrophages and the structural similarity among caspase family members. Herein, we designed and developed an efficient surface-enhanced Raman scattering (SERS) nanosensor for the highly sensitive, selective, and precise monitoring of dynamic caspase-1 level changes in macrophages during pyroptosis. The nanosensor was constructed by assembling a peptide chain containing the Raman reporter molecule 4-PB onto Au@Au core-shell nanoparticles. This peptide chain can be specifically recognized and cleaved by caspase-1, causing the reporter molecule 4-(phenylethynyl)benzenethiol (4-PB) to detach from the surface of the Au@Au core-shell nanoparticles and thereby reducing the intensity of its fingerprint peaks (2212&#xa0;cm^− 1) located in the cellular Raman-silent region, which enables highly specific and accurate detection of caspase-1. The plasmonic enhancement effect generated within the nanogaps of the core-shell nanoparticles significantly improves the detection sensitivity for caspase-1. We successfully monitored the dynamic changes of caspase-1 in macrophages during adenosine triphosphate (ATP)-induced pyroptosis. This SERS-based nanosensing strategy holds promise for detecting the activity of caspase family members in living cells and may provide an important scientific reference for the diagnosis and prognostic assessment of related diseases.</p> Graphical Abstract <p></p>