This letter describes the maskless fabrication of nanowells on a silicon substrate using chemically reactive nanoparticles. The amidine-functionalized polystyrene latex (APSL) colloids are adhered onto a silicon wafer, and hydrolysis of the particles' amidine groups generates the ammonium hydroxide etchant locally. The localized release of reactive species and its fast diffusion into the bulk liquid ensure that the silicon etching takes place only under the APSL colloids. Thus, the basal length of the nanowells is precisely controlled by the diameter of the APSL particles. The shape of the nanowells depends on the structure of the substrate: inverted pyramids on silicon (100) and hexagonal pits on silicon (111). The method described here provides an easy, inexpensive, safe, and high-throughput approach for generating nanowells on silicon surfaces. This maskless and simple nanofabrication method will open doors for new applications with locally generated or locally delivered chemistry from nanoparticles.