The interaction of lysozyme (Lyz)-conjugated silver (Ag) nanoparticles with (-)-epigallocatechin gallate (EGCG), one of the major components of green tea, has been investigated. Interaction of a protein with ligand/drug molecules perturbs the conformation of secondary and tertiary structures of the protein. We have demonstrated the conformational changes in the tertiary structures of the Lyz molecules on EGCG binding using surface-enhanced Raman scattering (SERS) and circular dichroism (CD) spectroscopic measurements. From the analysis of the amide I band of Lyz in SERS and CD spectra, the site of interaction of EGCG with protein molecules in Lyz-conjugated Ag particles has been identified. Spectroscopic evidence for the conformational response of Trp62 and Trp63, in the β-domain of the protein, to the binding of EGCG has been discussed.