Coomassie brilliant dyes have high affinity to proteins and high Raman activity, and on the basis of which, we have employed brilliant blue R-250 (BBR) and brilliant blue G-250 (BBG) as surface-enhanced Raman scattering (SERS) labels to probe protein-ligand recognitions. This method differs from previously proposed methods in that target proteins are labeled rapidly before biological recognitions without procedures of separation and purification, rather than attaching Raman labels to metal nanoparticles, which significantly simplifies the Raman dye labeling procedure. In typical assays, ligand-functionalized metal nanoparticles assemble by target protein-specific bindings and this assembly sequentially turns on electromagnetic enhancement of Raman scattering of the proposed labels. The method with its advantages of rapidness, high sensitivity, and spectral multiplexing has great potential in probing protein-protein and protein-small molecule recognitions not only in solution systems but also on flexible solid substrates.