Selenium is an essential micronutrient which functions as an essential constituent of selenoproteins. The selenoproteins play an important role in the body’s defense from free radicals associated with chronic diseases such as cancer. The effect of selenium on colon carcinogenesis was investigated using an experimental animal model. Five-week old ICR mice were acclimated for one week, and fed on the Fe-overloaded diet (450 ppm) with different Se diets (0.02, 0.1 or 0.5 ppm) for 12 weeks. Animals were injected intraperitoneally with azoxymethane (AOM, 10 mg/㎏ B.W. weekly for 3 weeks), followed by 2% dextran sodium sulfate (DSS) in the drinking water for a week. There were three experimental groups including low Se group (Lse), medium (normal standard diet for mice) Se (MSe), and high Se (HSe). The numbers of aberrant crypt foci (ACF) and aberrant crypt (AC) were measured in the colonic mucosa. The iron and selenium concentrations in liver was measured using ICP-AES. Glutathione peroxidase (GPx) activity was determined in the liver and colon. TUNEL assay for cell apoptosis and proliferating cell nuclear antigen (PCNA) staining for cell proliferation were performed. Immunohistochemical staining of β-catenin was also performed in mucous tissue of colon. The dietary Se decreased the numbers of ACF/㎠ and AC/㎠ in a dose-dependent manner. HSe diet significantly decreased the numbers of AC/㎠, compared with LSe diet (p<0.05). The tumor incidence rate in low Se diet group was 5% higher than medium Se diet group and 20% higher than high Se diet group. The activities of GPx in the liver and colon were dependent on the content of dietary selenium. Apoptosis-positive cells were also increased by dietary Se in a dose-dependent manner. PCNA-positive staining was weak in high Se group. β-catenin stained area was increased in low Se group while it was decreased in high Se group. These findings indicate that dietary selenium exert a protecting effect on colon cancer by inhibiting the development of ACF/AC, increasing GPX and apoptosis, and decreasing cell proliferation and expression of β-catenin in mice.