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To effectively shield the full band of ultraviolet (UV) radiation and provide desirable protection, the combination of inorganic and organic filters was often used to protect human skin from the serious harm of UV exposure. However, the incompatibility of different filters and their mutual negative effect limit the production of multifilter sunscreen. In addition, the hazard of reactive oxygen species (ROS) produced by inorganic filters after UV exposure and the skin permeability of organic filters remain unresolved problems. In this study, titanium dioxide (TiO2) and diethylamino hydroxybenzoyl hexyl benzoate (DHHB), two kinds of common filters with complementary UV shielding range, were first encapsulated into large mesoporous silica nanoparticles (MSN, ∼300 nm) to obtain MSN-TiO2 and MSN-DHHB. Also, a SiO2 coating was then made to seal and stabilize the MSN-TiO2 and MSN-DHHB. The structure, UV screen function, and safety of the SiO2-coated filters, MSN-TiO2@SiO2 and MSN-DHHB@SiO2, were evaluated. The good mechanical stability exhibited by the solid SiO2 layer prevented the release and skin penetration of the sealed DHHB and the photocatalysis of TiO2. Furthermore, the combination of MSN-TiO2@SiO2 and MSN-DHHB@SiO2 in sunscreen cream showed excellent UV shielding performance on covering the whole UV radiation range without mutual interference. Therefore, coating SiO2 over MSN is a feasible strategy for entrapping various filters to improve their photostability, preventing skin penetration and ROS generation, and enhancing their compatibility with different sunscreen formulations.