This research focuses on preparing a series of new TiO2/Ag hybrid aerogels with varying TiO2 contents, and demonstrates their application as ultrasensitive SERS substrates. The synthesized TiO2/Ag hybrid aerogels exhibited excellent SERS behavior when detecting 4-Mercaptobenzoic acid (4-MBA), and the calculated SERS enhancement factor (EF) was 6.34 × 106. 3D structured aerogels can create more hot spots and adsorption sites, and multiple interband chemical transfer (CT) pathways emerged and enhanced CT efficiency because of the large number of surface oxygen vacancies of meso-TiO2 NPs. Therefore, the synergy of electromagnetic field enhancement and chemical enhancement leads to SERS enhancement. In addition, the composite SERS substrate has high sensitivity, and the detection limit of adsorbed 4-MBA probe molecules reaches 10-11 M. Furthermore, the TiO2/Ag hybrid aerogels demonstrate good reproducibility with minimal standard deviation in terms of SERS signals. In addition, even after standing for 6 months, there is almost no attenuation in the SERS signal intensity, which highlights the excellent stability of this substrate. Therefore, these highly sensitive TiO2/Ag hybrid aerogels SERS substrates have important practical value in environmental monitoring, medical inspection and food supervision.