Due to notable water–salt activities, salt damage easily recurs and becomes one of the biggest challenges for the protection of ancient murals. Herein, superhydrophobic SiO2 materials with different sizes were used to modify mural ground layer substrates, and the improvement effect mechanisms were systematically evaluated with scanning electron microscopy (SEM), X-ray diffraction (XRD), laser scanning confocal microscopy (LSCM), and a contact angle instrument. The results show that the superhydrophobic SiO2 can spread into the substrates though holes and cracks and further increase the contact angles of the substrates to water droplets. Compared with the initial ground layer substrate, the substrates treated with the superhydrophobic SiO2 possess stronger mechanical strength and a better ability in suppressing water–salt activity. In particular, larger-size SiO2 (mSiO2) maintains better mechanical reinforcement in the substrates, because mSiO2 can provide better support in the internal gaps of the substrates. By contrast, nSiO2 can spread deeper into the substrate than mSiO2, and more greatly improve the contact angle to water droplets, endowing nSiO2 with a better ability to restrain water–salt activity. Our study provides an alternative idea for solving salt damage in murals, and promotes the application of SiO2 materials in heritage conservation.