We present a detailed analysis of the surface-enhanced Raman scattering (SERS) of adenine and 2′-deoxyadenosine 5′-monophosphate (dAMP) adsorbed on an Ag20 cluster by using density functional theory. Calculated Raman spectra show that spectral features of all complexes depend greatly on adsorption sites of adenine and dAMP. The complexes consisting of adenine adsorbed on the Ag20 cluster through N3 reproduce the measured SERS spectra in silver colloids, and thus demonstrated that adenine interacts with the silver surface via N3. We also investigate the SERS spectrum of adenine at the junction between two Ag20 clusters and demonstrate that adenine can bind to the clusters through N3 and the external amino group, while dAMP can be adsorbed on the cluster in an end-on orientation with the ribose and phosphate groups near to or away from the silver cluster. In contrast to the adenine–Ag20 complexes, the dAMP–Ag20 complexes produce new and strong bands in the low- or high-wavenumber region of the Raman spectra, due to vibrations of the ribose and phosphate groups. Furthermore, the spectrum of dAMP bound to the Ag20 cluster via N7 approaches the experimental SERS spectra on silver colloids.