Abstract: Organic filters in conventional sunscreens generally have poor photo stability and can easily penetrate through stratum corneum and dermis into the blood vessel, thus causing potential health-threatening issues. Polydopamine (PDA) nanoparticles can be formed by self-polymerization of dopamine. Inspired by its excellent anti-ultraviolet, free radical scavenging and adhesion properties, the titanium dioxide (TiO₂) precursor is prepared by the sol-gel method and blended with dopamine hydrochloride to prepare PDA-TiO₂ hybrid nanoparticles. Infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), ultraviolet-visible absorption spectroscopy (UV-Vis), thermogravimetric analysis (TGA) and skin penetration experiments were used to characterize the basic structures and properties of nanoparticles. Under the synergistic effect of PDA and TiO₂, the particles have highly efficient UV protection. By simply adjusting the reaction material ratio, it was found that the more dopamine content, the better UV absorption effect was obtained, and it showed better UV absorption performance than small particle size PDA. Therefore, PDA-TiO₂ (1/10) (m (DA)∶m(TiO₂)=1∶10) had the best UV absorption effect. The PDA-TiO₂ (1/10) was introduced as the sole active ingredient to formulating sunscreen, whose sun protection factor (SPF) values could reach 33.7, which can meet daily sun protection needs. Most importantly, PDA had good bioadhesion and can effectively prevent the penetration of PDA-TiO₂ hybrid nanoparticles. The thickness of the stratum corneum of the human body was about 15—20 μm. Upon comparing the PDA-TiO₂ with commercially available benzophenone small molecule sunscreens, it was found that the skin permeability of PDA-TiO₂ was significantly reduced. The penetration depth was 9—17 μm, mainly distributed in the upper and middle parts of the stratum corneum of the skin. It is not easy to enter the human body and will not pose a potential threat to skin health. The commercially available benzophenone sunscreen small molecules had a skin penetration of 18—35 μm, indicating that they penetrate the stratum corneum to reach the living epidermis and enter the human body. Therefore, the prepared nanoparticles have excellent UV resistance and biocompatibility, ensuring their excellent performance and safe use in sunscreens.