Programmed cell death (PCD) is decisive in eliminating affected cells in human cancers, whereas there are increasing cases of cancer-related death due to side effects of modern treatment methods. There is an urge for new methods of growth inhibition and elimination of cancer cells with a lower cytotoxicity to normal cells. Irregularity along PCD pathways plays a crucial role in cancer cell carcinogenesis. Apoptosis is a distinct cell death mechanism occurring in multicellular organisms and also called type one programmed cell death. Autophagy and paraptosis are non-apoptotic PCD occurring in multicellular organisms. Natural compounds are the fundament of pharmacological treatments, and flavonoids are natural polyphenolic compounds which are unique due to their diverse chemical structures and various biological active mechanisms like anticancer, anti-inflammatory, antioxidative and much more. This gives an increasing number of studies indicating that some flavonoids from medicinal plants could be promising candidates for new natural anticancer drugs, which attract high interests of academic researchers and advanced users. An understanding of the underlying mechanism of PCD induced by flavonoids in cancer cells is important as it plays a pivotal role in the pathogenesis of many diseases. This systematic review is to report flavonoids and their derivatives as new anticancer candidates to stimulate PCD with a different mechanism based on the pharmacological evidence.