Implant-associated infections caused by the formation of bacterial biofilms on the implant surface are difficult to cure, which will lead to poor integration between soft tissues and percutaneous implants. To solve this issue, in this work, cerium-based metal-organic framework (Ce-BTC) coatings with abundant coordinative unsaturated metal sites were fabricated on medical titanium surfaces by solvothermal treatment and followed by hydrogen plasma immersion ion implantation (H-PIII) treatment. The surface microstructure of Ce-BTC had no obvious changes after H-PIII treatment, while the crystallinity reduced and the organic ligands were partially etched, resulting in more metal active sites being exposed. Consequently, adenosine triphosphate (ATP) deprivation capacity and oxidase-like activity of Ce-BTC were significantly improved by H-PIII treatment, which could effectively prevent biofilm formation and kill bacteria in response to the bacteria-mediated acidic microenvironment. Moreover, the Ce-BTC treated by H-PIII for 15 min could promote the fibroblast responses including cell proliferation and collagen deposition by up-regulating fibroblast-related genes in vitro, which may be ascribed to the surface nanorod structures and the released Ce ions. The percutaneous infection model in vivo further confirmed that the Ce-BTC treated by H-PIII for 15 min had good antibacterial activity and soft tissue sealing ability, which was conducive to the integration between percutaneous implants and surrounding soft tissues.