In this work, a simple and facile strategy was developed for the fabrication of large sized Au spherical architectures (AuSAs) with flexible nanoflakes as subunits by using a liquid-liquid interfacial reaction route at room temperature. The as-prepared AuSAs were characterized and analyzed by scanning electron microscopy, X-ray powder diffraction, thermogravimetric analysis and transmission electron microscopy. The effects of a series of factors on the morphologies and structures of the products were studied in detail. On the basis of control experiments and molecular dynamics simulations, a possible growth mechanism was suggested for the formation of AuSAs at the interface between toluene and water. Furthermore, due to the relatively large particle size, high surface roughness and high symmetry of the spherical characteristics, AuSAs could be used to perform individual particle SERS investigation, which demonstrated remarkable SERS responses and high reproducibility. Fig. 9 (a) SERS spectra of R6G adsorbed on five randomly chosen AuSAs; (b) SERS spectra of melamine adsorbed on AuSAs with different concentrations: 1, 10 À4 M; 2, 10 À5 M; 3, 10 À6 M; and 4, 10 À7 M.