We report a simple method of enhancing the chemical stability of monothiol-modified oligonucleotide–gold and –silver nanoparticle conjugates by a thin silica reinforcement coating. Conventional conjugates prepared by chemisorption of monothiol-modified oligonucleotides onto nanoparticle surfaces undergo rapid aggregation in the presence of thiol-containing small molecules (e.g., dithiothreitol) due to ligand exchange reactions. When the conjugates are treated with (3-mercaptopropyl)trimethoxysilane, a thin silica layer is formed on the nanoparticle surface, thereby entrapping and reinforcing the thiol–gold/–silver linkage. These silica-modified oligonucleotide–gold and –silver nanoparticle conjugates become much more stable toward dithiothreitol as compared to the unmodified conjugates. Moreover, the silica layer significantly hinders the gold/silver core from oxidative dissolution by sodium cyanide. Importantly, the unique hybridization-induced color change property of the oligonucleotide–gold and –silver nanoparticle conjugates is preserved even under harsh condition (i.e., high concentrations of dithiothreitol). Taken together, these ultra-stable oligonucleotide–nanoparticle conjugates hold promise for new diagnostics and therapeutics.