This work is related to the investigation of the effects of porous silicon (PSi) morphologies on the performance of plasmonic gold nanoparticles (Au-NPs) hot spot SERS sensors for the detection of amoxicillin molecules. Two Si wafers with different resistivity values of 10 and 100 Ω.cm were used to synthesize a PSi layer of pores- and mud-like structures, respectively, by pulsed photo chemical etching process. The hot spot SERS sensors were synthesized by incorporating the Au-NPs within the PSi morphologies of pores- and mud- like structures which are characterized by high density of nucleation sites. Plasmonic Au- NPs with different sizes and hot spot regions were incorporated into the porous structures by the ion reduction process. It was recognized that the PSi morphologies have a considerable influence on the fabrication process of the detection sensors and, consequently, on the detection process. The plasmonic Au-NPs hot spot SERS sensor based on the PSi morphology of the mud-like structures shows higher sensitivity than that of pores-like structures, even at very low concentrations of amoxicillin solutions.