In the current study, we investigated the antimicrobial effect of titanium hydroxyapatite (TiHA), a photo-oxidizing organic material, in denture base resin on single-species biofilms formed by laboratory bacteria and on multispecies biofilms formed by bacteria from the human saliva. Although TiHA reportedly restricts the growth of planktonic bacteria upon ultraviolet A (UVA) irradiation, the antimicrobial effect of TiHA on bacterial biofilms remains to be elucidated. Resin specimens were prepared by adding TiHA to polymethyl methacrylate-based, denture base resin. The specimens were incubated with biofilm-forming Streptococcus sanguinis, Actinomyces naeslundii, Staphylococcus aureus, Escherichia coli, or bacteria from the human saliva obtained from volunteers. After UVA irradiation, the colony-forming units (CFUs) from the biofilms formed on the specimens were determined. CFU numbers for S. sanguinis, A. naeslundii, and S. aureus that formed biofilms on TiHA-containing specimens were significantly lower than those formed on specimens without TiHA. TiHA did not reduce the CFUs of biofilm-forming E. coli. In all cases, CFU numbers in the biofilms formed on TiHA-containing specimens by the salivary bacteria were significantly reduced. In addition, neither a 56 h UVA irradiation nor a 28 d soaking in water diminished the antibacterial effect of TiHA. TiHA in denture base resin exerts an antimicrobial effect on single-species bacterial biofilms and biofilms formed by a wide variety of bacteria from human saliva.