Cancer is the third cause of death worldwide, with complex etiology, and is defined as an uncontrolled growth of cells. A high proportion of cancer incidence and deaths are due to different environmental and genetic factors such as high body mass index, low fruit and vegetable intake, lack of physical activity, tobacco use, alcohol consumption, exposure to radiation, chronic infections, and heredity also. In addition, oxidative stress plays a crucial role in the pathophysiology of different types of cancer. Hence, screening and testing of more effective compounds with minimum side effects for the prevention and treatment of cancers started a few decades ago. Regarding this, much attention has been paid to natural antioxidants as a novel prevention and treatment strategy for cancer. Flavonoids are one of the most important ingredients in vegetables and fruits, especially in the genus Citrus. Hesperidin is a flavonone glycoside, belonging to the flavonoid family, which is widely found in Citrus species and acts as a potent antioxidant and anticancer agent. In the present review, we attempt to provide an overview and summarize the scientific literature about the cancer chemoprotective effects of hesperidin with an emphasis on its relation to the protection roles against oxidative stress.