Gold-silica (Au-SiO2) nanohybrids are of great technological importance, and it is crucial to develop facile synthetic protocols to prepare Au-SiO2 nanohybrids with novel structures. Here we report the bioinspired synthesis of pomegranate-like SiO2@Au nanoparticles (P-SiO2@Au NPs) via one-step aqueous synthesis from chloroauric acid and tetraethyl orthosilicate mediated by a basic amino acid, arginine. Effects of chloroauric acid, tetraethyl orthosilicate, and arginine on the morphology and optical property of the products are investigated in detail. The P-SiO2@Au NPs achieve tunable plasmon resonance depending on the amount of chloroauric acid, which affects the size and shape of the P-SiO2@Au NPs. Finite-difference time-domain simulations are performed, revealing that the plasmon peak red-shifts with increasing particle size. Arginine serves as the reducing and capping agents for Au as well as the catalyst for SiO2 formation and also promotes the combination of Au and SiO2. Formation process of the P-SiO2@Au NPs is clarified through time-course analysis. The P-SiO2@Au NPs show good sensitivity for both colloidal and paper-based surface-enhanced Raman scattering measurements. They achieve enhancement factors of 4.3 × 107-8.5 × 107 and a mass detection limit of ca. 1 ng using thiophenol as the model analyte.