Tyrosine (Tyr) is involved in the synthesis of neurotransmitters, catecholamines, thy-roid hormones, etc. Multiple pathologies are associated with impaired Tyr metabolism. Silver nanoclusters (Ag NCs) can be applied for colorimetric, fluorescent, and surface-enhanced Raman spectroscopy (SERS) detection of Tyr. However, one should understand the theoretical basics of interactions between Tyr and Ag NCs. Thereby, we calculated the binding energy (E_b ) between Tyr and Ag_n^q (n = 1–8; q = 0–2) NCs using the density functional theory (DFT) to find the most stable complexes. Since Ag NCs are synthesized on Tyr in an aqueous solution at pH 12.5, we studied Tyr⁻¹, semiquinone (SemiQ⁻¹ ), and Tyr⁻² . Ag₃²⁺ and Ag₅⁺ had the highest E_b . The absorption spectrum of Tyr⁻² significantly red-shifts with the attachment of Ag₃²⁺, which is prospective for colorimetric Tyr detection. Ag₃²⁺ interacts with all functional groups of SemiQ⁻¹ (phenolate, amino group, and carboxylate), which makes detection of Tyr possible due to band emergence at 1324 cm⁻¹ in the vibrational spectrum. The ground state charge transfer between Ag and carboxylate determines the band emergence at 1661 cm⁻¹ in the Raman spectrum of the SemiQ⁻¹ –Ag₃²⁺ complex. Thus, the prospects of Tyr detection using silver nanoclusters were demonstrated.