The incidence of cancer can be decreased by avoiding the intake of mutagens and carcinogens; however, cancer is also induced by endogenous factors. Water is the most essential substance for life, but causes DNA damage via the release of purine nucleobases from DNA, termed depurination, and the hydrolysis of amino groups of nucleobases, termed deamination. Nitric oxide and hypochlorous acid, essential compounds in the host defense system, are formed by specific enzymes and kill invading microorganisms. Nitric oxide reacts with nucleobases resulting in deamination products as well as hydrolysis. Recently, two novel products were identified in the reaction of nucleobases with nitric oxide. Hypochlorous acid reacts with nucleobases resulting in various products. In addition, several products including novel compounds have been identified in the reaction of hypochlorous acid with guanine. When DNA replication occurs without complete repair, these lesions cause mutations in cellular DNA, and accumulation of these mutations may cause cancer. Thus, we should consider water, nitric oxide, and hypochlorous acid in the human body as endogenous cancer risk factors. This review describes DNA damage and subsequent mutations caused by water, nitric oxide, and hypochlorous acid.