To investigate the radioprotective effect of the combination of famotidine and vitamin C against radiation-induced micronucleus formation in mouse bone marrow erythrocytes, various doses of famotidine or vitamin C or combinations thereof were administered intraperitoneally to adult male NMRI mice 2 h before 2 and 4 Gy γ-irradiation. The frequency of micronucleated polychromatic erythrocytes (MnPCEs) was scored in 5,000 polychromatic erythrocytes (PCEs), and the cell proliferation ratio [PCE/(PCE + NCE); NCE = normochromatic erythrocytes] was also calculated for each treatment group. Data were statistically evaluated using one-way ANOVA test. The results show that pretreatment with various doses of famotidine and vitamin C before γ-irradiation significantly reduced the frequency of MnPCEs with a protection factor (PF) of 2 and 1.7, respectively. Pretreatment with vitamin C also significantly increased the cell proliferation ratio, while famotidine had no effect. Combination of famotidine and vitamin C was more effective in reducing MnPCEs than each compound alone, leading to a PF of 4.3 after irradiation. Cell proliferation ratio was also significantly improved by the combination compared with the irradiated control groups. Both famotidine and vitamin C are potent scavengers of free radicals and reactive oxygen species, especially OH(·). The combination of the two compounds probably further enhances this activity, thus leading to high bone marrow protection.