Colorectal cancer is the second leading cause of cancer-related deaths in the United States with an expected 51,020 deaths in 2019 from colon cancer alone (American Cancer Society 2019). Evidence from epidemiological, early clinical, and preclinical studies suggested that dietary supplementation with the essential trace mineral selenium (Se) reduces the incidence of and mortality from colon cancer (Jacobs et al. 2004). However, a more recent human clinical trial did not conclude protection against colon or other cancers in a population with high baseline plasma Se levels (Lippman et al. 2009). This finding clearly demonstrates the need for further basic research on molecular mechanism behind the potential effects of Se in cancer (Hatfield & Gladyshev 2009). Primarily, Se appears to mediate its biological functions through selenoproteins, whereas the effect of Se intake on tissue expression of most selenoproteins has been established, if and how Se exerts epigenetic effects on or via selenoproteins, especially those that have been implicated in both prevention and promotion of cancers, remains to be elucidated.