Nanostructured materials with designable microstructure and controllable physical and chemical properties are highly desired for practical applications in nanotechnology. In this article, it is reported that nanoporous copper with a tunable nanopore size can be fabricated by controlling the dealloying process. The influence of acid concentration and etching potential on the formation of nanoprosity is systematically investigated. With optimal etching conditions, the nanopore sizes can be tailored from ∼15 to ∼120 nm by controlling the dealloying time. It is found that the tunable nanoporosity leads to significant improvements in surface-enhanced Raman scattering (SERS) of nanoporous copper and peak values of SERS enhancements for both rhodamine 6G and crystal violet 10B molecules are observed at a pore size of ∼30–50 nm. This study underscores the effect of complex three-dimensional nanostructures on physical and chemical properties and is helpful in developing inexpensive SERS substrates for sensitive instrumentations in molecular diagnostics.