Computational approaches within the framework of density functional theory (DFT) were employed to elucidate the binding mechanism of the cysteine amino acid on silver nanoparticles using several small silver clusters Agn with n = 2−10 as surface models. The long-range corrected LCBLYP functional and correlation consistent basis sets cc-pVTZ-PP and cc-pVTZ were used to determine the structural features, energetics, and spectroscopic and electronic properties of the resulting complexes. In vacuum and highly acidic conditions, cysteine molecules prefer to adsorb on silver clusters via their amine group. In aqueous solution, the thiolate head turns out to be the most energetically favorable binding site. The cysteine affinity of silver clusters is greatly altered in different conditions, i.e., acidic solution < vacuum < aqueous solution, and is strongly dependent on the cluster size. As compared to free clusters, the frontier orbital energy gap of the ones capped by cysteine is significantly improved, which corresponds to stronger stability, especially in aqueous solution. The analysis of frontier orbitals also reveals that both forward and backward electron donations exhibit comparable contributions to the enhancement of stabilizing interactions. As for an application, a chemical enhancement mechanism of the surface-enhanced Raman scattering (SERS) procedure of cysteine by silver clusters was also analyzed.