Apigenin (APG) is a flavonoid presence in beverages, vegetables, and fruits containing anti-diabetic, anti-oxidant, and anti-viral activities, as well as cancer management properties. There is growing evidence that APG presented extensive anti-cancer effects in several cancer types by modulating various cellular processes, including angiogenesis, apoptosis, metastasis, autophagy, cell cycle, and immune responses, through activation or inhibition of different cell signaling pathways and molecules. By emerging nanotechnology and its advent in the biomedicine field, cancer therapy has been changed based on nanotechnology-based delivery systems. APG nanoformulations have been used to target tumor cells specifically, improve cellular uptake of APG, and overcome limitations of the free form of APG, such as low solubility and poor bioavailability. In this review, the biotherapeutic activity of APG and its mechanisms, both in free form and nanoformulation, toward cancer cells are discussed to shed some light on APG anti-tumor activity in different cancers.