In this work, we combined a hierarchical nano-array effect of silicon nanowires (SiNWs) with a metallic surface of silver nanoparticles (AgNPs) to design a surface-enhanced Raman spectroscopy (SERS) scattering substrate for sensitive detection of Rhodamine 6G (R6G) which is a typical dye for fluorescence probes. The SiNWs were prepared by Metal-Assisted Chemical Etching (MACE) of n-Si (100) wafers. The Doehlert design methodology was used for planning the experiment and analyzing the experimental results. Thanks to this methodology, the R6G SERS response has been optimized by studying the effects of the silver nitrate concentration, silver nitrate and R6G immersion times and their interactions. The immersion time in R6G solution stands out as the most of influential factor on the SERS response.