<p>Flavonoids are naturally occurring secondary metabolites in plants that possess biological activities and are beneficial for treating various diseases, including cancer. They are predominantly produced in plants and are used to target multiple molecules at the cellular level or processes at the systemic level. These molecules exhibit several properties, such as anti-inflammatory, antioxidant, anti-proliferation, anti-tumor and anti-metastatic, which can be used to target and destroy cancer cells. To manifest these properties, flavonoids interact directly or indirectly with the biomolecules of life. Nucleic acids are among the most important biomolecules, serving as carriers of hereditary information. Any damage or alteration in nucleic acid function directly impacts cellular function and, consequently, cell proliferation. In this review, we describe the ways in which various flavonoids interact with nucleic acids. The interactions are categorized into direct and indirect mechanisms that can be utilized to investigate the potential anti-cancer targeting properties of flavonoids.</p>