The application of antibacterial in leather and leather articles is of great value, but has not been considered widely, while the use of it in the textile and plastic is somewhat popular. In order to maintain a good antibacterial activity and overcome the defects of antibacterial agents of the quaternary ammonium salts, nano-fumed silica derivative with quaternary ammonium groups (NFSQA) was prepared and used in the finishing of leather for the making of antibacterial leather in this report. The application scheme of the antibacterial agent coupled with finishing agents and the antibacterial effect of it were researched. When the polyacrylate resin/the polyurethane binder was mixed with NFSQA, there was a stronger trend of cohesion, and the antibacterial activity of NFSQA to E. coli and S.aureus was decreased. This was due to the strong interaction between the poly-cationic macromolecular NFSQA and the macromolecular polymer, and the formation of wrap and seclusion around NFSQA that results in the absence of enough antibacterial points of NFSQA on the surface of the finishing leather. Besides, the interaction may also weaken the antibacterial activity of the cationic NFSQA. Furthermore, the leather coated with the mixture of NFSQA, polyacrylate, and polyurethane had no antibacterial activity, due to the further action of wrap and seclusion of the formed polymer membrane to NFSQA. The polysiloxane auxiliary and the finishing agent nitrocellulose had no influence on the antibacterial activity of NFSQA to E.coli and S.aureus in substance, when they were mixed with it, respectively. The polysiloxane auxiliary and the nitrocellulose were different from the polymer filmerformers. There were no the phenomena of cohesion in their mixture and the action of wrap and seclusion in the compact film. The protein binder had influence on the antibacterial activity of NFSQA, but its influence was weaker than that of the polymer binders. Maybe this should distribute to the poor filming ability it.