Owing to its high sensitivity, surface-enhanced Raman spectroscopy (SERS) is largely used in biosensing as an efficient optical technique. In this work, we report the elaboration of a novel SERS substrate based aptasensor for ultra-sensitive and selective detection of prostate specific antigen (PSA). The SERS substrate is based on silicon nanowires (SiNWs) as transducer surface coated by silver nanoparticules (AgNPs). The silver nanoparticles have two purposes : a) aptamer immobilization via thiol chemistry and b) Raman signal enhancement. The presence of PSA induces the appearance of amide vibration modes only if the aptamer is present on the surface of SiNWs. The platform is highly sensitive, selective and specific to PSA in a wide range of concentrations from 0.1 to 20 µg.L-1 with a detection limit of 0.1 µg.L-1 , which encompasses the blood serum range of healthy subjects and ill patients. This optical biosensor shows a great stability and it is successfully validated in human blood serum samples showing very good results.