Surface-enhanced Raman spectroscopy (SERS) has been considered a promising technique for the detection of trace molecules in biomedicine and environmental monitoring. The ideal metal nanoparticles for SERS must not only fulfill important requirements such as high near-field enhancement and a tunable far-field response but also overcome the diffusion limitation at extremely lower concentrations of a target material. Here, we introduce a novel method to produce gold nanoparticles with open eccentric cavities by selectively adapting the structure of non-plasmonic nanoparticles via acid-mediated surface replacement. Copper oxide nanoparticles with open eccentric cavities are first prepared using a microwave-irradiation-assisted surfactant-free hydrothermal reaction and are then transformed into gold nanoparticles by an acidic gold precursor while maintaining their original structure. Because of the strong near-field enhancement occurring at the mouth of the open cavities and the very rough surfaces resulting from the uniformly covered hyperbranched sharp multi-tips and the free access of SERS molecules inside of the nanoparticles without diffusion limitation, adenine, one of the four bases in DNA, in an extremely diluted aqueous solution (1.0 pM) was successfully detected with excellent reproducibility upon laser excitation with a 785-nm wavelength. The gold nanoparticles with open eccentric cavities provide a powerful platform for the detection of ultra-trace analytes in an aqueous solution within near-infrared wavelengths, which is essential for highly sensitive, reliable and direct in vivo analysis.