A new chromogenic chemosensor based on lysine-functionalized silver nanoparticles 1 was prepared, and characterized by transmission electron microscopy (TEM), Fourier transform. Raman, and ultraviolet-visible (UV-vis) spectroscopy. The color changes of nanoparticles 1 in the absence and the presence of metal ion were observed, upon addition of various amino acids and proteins in aqueous solution. Among the various amino acids, the sensor 1 in the absence of metal ion shows a novel colorimetric sensor with capability to probe histidine and histidine-tagged proteins. On the other hand, the color changes of 1 in the presence of metal ions such as KCl or NiCl2 did not occur with any amino acids. Therefore, the sensor 1 in the absence of metal ion responds selectively to histidine, a response which can be attributed to its aggregation induced by histidine with high numbers of electrostatic interactions. This highly selective sensor 1 allows a rapid, quantitative assay of histidine to concentrations as low as 5.0 μM, providing a new tool for the direct measurement of histidine and histidine-tagged proteins in vitro system. Furthermore, we examined the effect of pH on absorbance (A520) of 1 in the presence of histidine (pH 4-12). The absorbance under basic conditions was higher than that under acidic or neutral conditions, in accord with the stronger aggregation of 1 with histidine by electrostatic interaction between the carboxylate anion of 1 and ammonium protons of histidine under basic conditions.