Core-shell structured Au NRs with a surface-exposed gold core and a mesoporous silica shell (MS Au NRs) were demonstrated as a promising platform for localized surface plasmon resonance (LSPR) based molecular sensing. Mesoporous silica shell not only allows the Au NRs core to be directly exposed to their surrounding environment but also stabilizes Au NRs dispersion in various water-organic mixtures and pure organic solvents. The LSPR band of MS Au NRS displays a stable and linear response in spectral shift to the changes in their surrounding refractive index with a sensitivity of 325 nm/RIU. To demonstrate the application of MS Au NRs as LSPR nanosensors in molecular sensing, the plasmon response to molecular adsorbates (GSH) was demonstrated. MS Au NRs provide a more stable and sensitive response than CTAB-capped Au NRs in GSH sensing. In addition, we have also demonstrated that the LSPR response of Au NRs is highly sensitive to changes of local refractive index in mesoporous silica shell, which renders the feasibility of using MS Au NRs as effective molecule-sensing platforms when mesoporous silica shells were functionalized with various chemical and biological ligands.