Background: In boron neutron capture therapy (BNCT), the intravenous administration of boron-containing compounds such as boronophenylalanine (BPA) and borocaptate sodium (BSH) is followed by irradiation with thermal neutrons. In the present study, we determined whether a boron-rich boron carbide (B4C) nanoparticle could be used for BNCT. Methods: B4C nanoparticles were obtained by the laser fragmentation of boron particles in ethyl acetate. Neutron irradiation was delivered via a neutron beam at the Kyoto University Research Reactor (KUR). Results: Cell viability was lower in oral squamous cell carcinoma (SCC) cells exposed to neutrons in the presence of B4C particles than in those exposed to neutrons only. The combination of B4C particles and neutron irradiation also decreased the formation of colonies.Injecting B4C particles into the oral SCC xenografts of nude mice increased the concentration of 10B in the tumors, but not in the kidney, liver, or spleen. The body weights of animals were not affected by neutron irradiation to B4C-injected tumors.Tumor volumes were lowerTumor volumes were lower in the B4C- mediated BNCT group than in the neutron group. Conclusion: These results indicate that B4C particles can be used locally as a boron compound in BNCT for oral SCC.