​Characterizing over-expressed enzymes or biomarkers in living cells is critical for the molecular understanding of disease pathology and consequently for designing precision medicines. Herein, a “switch-on” probe is designed to selectively detect γ-glutamyl transpeptidase (GGT) in living cells via a unique ensemble of enhanced fluorescence and surface enhanced Raman scattering (SERS). In the presence of GGT, the γ-glutamyl bond in the probe molecule is cleaved, thereby activating a fluorescent probe molecule as well as a Raman reporter molecule. Consequently, the detection of GGT is achieved based on both plasmonic fluorescent enhancement (PFE) and SERS with a limit of detection as low as 1.2 x10-3 U/L (normal range for GGT levels in blood is 9-48 U/L). The main advantage of this platform is that in the occasion of fluorescence signal interference, especially in the presence of floating metal ions in cells, the SERS signals still hold high stability as a backup. This work highlights the benefits of marrying two complimentary sensing techniques into one platform that can overcome the major obstacles of real-time biomarkers detection and imaging in living cells.