Here, we show that nanoparticles functionalized with oligonucleotides and Raman labels, coupled with surface-enhanced Raman scattering (SERS) spectroscopy, can be used to perform multiplexed detection of oligonucleotide targets (Scheme 1). Although oligonucleotides can be directly detected by SERS on aggregated particles (7, 8), the structural similarities of oligonucleotides with different sequences result in spectra that are difficult to distinguish. Therefore, researchers often use different Raman dyes to label different oligonucleotides to distinguish oligonucleotide sequences (9, 10). To realize the benefits of high-sensitivity and high-selectivity detection coupled with multiple labeling capabilities, we designed nanoparticle probes that can be used for DNA (or RNA) detection (Scheme 1). These probes consist of 13-nm-diameter Au particles functionalized with Raman dye-labeled oligonucleotides. The Raman spectroscopic fingerprint, which can be designed through choice of Raman label, can be identified after Ag enhancing by scanning Raman spectroscopy (Scheme 1). Because the SERS-active substrate in this strategy is generated immediately before the detection event, a large and reproducible Raman scattering response can be obtained.