Purpose: To apply titanium tetrafluoride (TiF4) in an aqueous solution or incorporated into the primer of a self-etching adhesive (Clearfil SE Bond) as dentin pre-treatment and evaluate its antimicrobial effect, determine the minimum bactericidal concentraion (MBC) against Streptococcus mutans and Lactobacillus casei and analyse its potential to inhibit the development of carious lesions at the restoration interface. Materials and Methods: For MBC, an aqueous solution or primer with different concentrations (in %) of TiF4 were used (from 0.0 to 4.0). Also, 50 cavities were prepared at the enamel/dentin junction of third molars and received the following dentin pre-treatments (n = 10): Clearfil SE Bond (CL); aqueous solution of 2.5% TiF4 + CL (T2.5%); aqueous solution of 4% TiF4 + CL (T4%); 2.5% TiF4 incorporated into the primer (P2.5%); 4% TiF4 incorporated into the primer (P4%). Cavities were restored and submitted to pH cycling to create artificial caries lesions. Microhardness tests were performed after sectioning the restorations to assess the demineralisation at margins. Results: ANOVA and Tukey's tests showed that TiF4 in aqueous solution presented MBC against S. mutans and L. casei of over 2.0%. TiF4 in the primer of a self-etching adhesive presented MBC of over 1% for L. casei. For enamel, CL showed no significant differences in microhardness between the depths. Conclusions: The aqueous solution had an antimicrobial effect against Streptococcus mutans and Lactobacillus casei of over 2.0%. Pretreatment with the aqueous solution or primer did not inhibit demineralisation at enamel or dentin restoration interfaces. Keywords: adhesive system, microhardness, microorganism, secondary caries, titanium tetrafluoride