CaCO3@mesoporous silica reacted with phosphoric acid (denoted as CCMS-HP) enables the growth of calcium phosphate crystals in dentinal tubules. This study tested whether CCMS-HP could be used to form a biomimetic barrier on the exposed dentin for prevention of dentin sensitivity without impairing the bonding of Single Bond Universal (SBU) self-etch adhesive to the dentin. Methods: Twenty-four dentin disks were prepared and divided into three groups: (1) SBU group (n = 8), in which SBU self-etch adhesive was bonded to the dentin disk directly; (2) CCMS-HP group (n = 8), in which CCMS-HP was applied onto the dentin surface; and (3) CCMS-HP/SBU group (n = 8), in which the dentin surface was first treated with CCMS-HP and then boned by SBU. The permeation depth of crystals into the dentinal tubules was examined and measured with a scanning electron microscope. The shear bonding strength of SBU and CCMS-HP/SBU to dentin was also measured. Results: The mean crystal permeation depth was 35.8 ± 6.9 μm for the CCMS-HP/SBU group and 33.6 ± 12.2 μm for the CCMS-HP group; no significant difference was found between the two groups. Moreover, the mean shear bonding strength was 22.7 ± 6.7 MPa for the CCMS-HP/SBU group and 23.3 ± 7.0 MPa for the SBU group. There was also no significant difference between the two groups. Conclusion: CCMS-HP can be used to form a biomimetic barrier for prevention of dentin sensitivity because it neither impedes the bonding of SBU to dentin nor impairs the shear bonding strength between the SBU and dentin.