Neoplastic diseases, whose incidence is on the increase, rank the second among the diseases in which oxidative stress and disturbances in the organism’s protective functions contribute to the development. The neoplastic process is a long-lasting and multi-level phenomenon. One of the main reasons for the initiation of carcinogenesis is DNA damage caused by mutagenic (genotoxic) factors, which include free radicals. This paper discusses the role of selenium in the risk and prevention of neoplastic diseases, based on a review of scientific reports and the results of studies conducted in different centers. The greatest biological significance of selenium is associated with its occurrence in enzymes and proteins. Moreover, it has been demonstrated that there is a strict correlation between the Se content in a diet and the incidence of neoplastic diseases and related mortality. Research evaluating medical applications of selenium has made significant progress, showing that the optimal level of selenium is correlated with a reduction in total mortality and cancer risk. Both excessively low and excessively high selenium concentrations are unfavourable. However, the optimal level of selenium varies and is population-dependent. This may be related to the contamination of the environment with different chemical compounds that are neutralized by selenium. Selenium decreases the risk of lung, urinary bladder, large intestine, liver, oesophagus, stomach and prostate neoplasms. A low selenium level in the blood, hair or nails may significantly increase the risk of neoplasms. It is possible to enhance the positive role of selenium in maintaining human health through the optimization of its content owing to research into genotypes.