Colorectal cancer is one of the most common types of cancer in men and women who consume a Western diet. We investigated the inhibitory effect of selenium (sodium selenite, Na2SeO3) and selenium nanoparticles (nano-Se) on experimental colon carcinogenesis in ICR mice. After a 1-week acclimation, 6-week-old mice received three intraperitoneal (i.p.) injections (experimental week 0-2) of azoxymethane (AOM, 10 mg/kg body weight, b.w.), followed by 2% dextran sodium sulfate (DSS)-containing drinking water for the next 1 week. The three groups (10 mice/group) were orally administered either distilled water (control), selenium (1.7 ppm), or nano-Se (1.7 ppm) daily for 8 weeks. The numbers of aberrant crypt foci (ACF), aberrant crypt (AC), and tumorous lesions were measured in colonic mucosa. Se and nano-Se treatments significantly decreased the number of ACF, AC, and tumorous lesions compared with the control. However, there was no significant difference between the selenium and nano-Se groups. The glutathione peroxidase (GSH-Px) activity in the liver and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity in serum, were high in the selenium and nano-Se groups, while thiobarbituric acid reactive substance (TBARS) level was low in both Se and nano-Se groups when compared with that in the control group. These findings indicate that selenium and nano-Se showed similar protective effects against colon carcinogenesis by inhibiting the development of ACF and tumorous lesions in mice.