Background: Lysozyme level in body fluids is a significant indicator of various diseases. Cheap and simple colorimetric detection of lysozyme, in biological sample, by gold and silver nanoparticles is a field of interest of nanoparticle research for more than a decade.Objective: We report here an attempt to improve the sensitivity part of the colorimetric lysozyme detection process by using citrate capped gold-silver core-shell nanoparticles without any functionalization. Methods: Performance of gold-silver core-shell nanoparticles in determining of lysozyme concentration in water is done using colorimetric/spectroscopic technique. Gold nanoparticles, silver nanoparticles and mixed colloidal suspension of gold and silver nanoparticles, for comparison have also been studied. Selectivity study has been performed through spectroscopic analysis, red-greenblue colour component analysis and fractal dimension analysis of the nanoparticles interacted with several low and high isoelectric point proteins. Results: Gold-silver core-shell nanoparticles showed higher sensitivity for a wider range of lysozyme concentration compared to gold and silver nanoparticles prepared by us or reported in literature. Gold nanoparticles showed higher sensitivity compared to the core-shell nanoparticles, but for a narrow concentration range of lysozyme. For silver nanoparticles and the mixed nanoparticle system, both sensitivity and range of determination of lysozyme concentration were much smaller compared to the core-shell nanoparticles. Core-shell nanoparticles showed better selectivity compared to gold nanoparticles in identifying aquatic solution of lysozyme from that of other proteins. Conclusion: Gold-silver core-shell nanoparticles have higher sensitivity in determining wide range of lysozyme concentration in water compared to gold and silver nanoparticles reported in literature.