Abstract: With population ageing and the great improvement in life following economic development, the burden (incidence and mortality) of malignant diseases is becoming heavier. The development of cancer is often caused by persistent inflammation, necrosis, and proliferation in targeted tissues and/or organs on the abasis of systemic, low-grade chronic inflammation. Factors facilitating this process are mostly the risk factors of cancer. Large-scale prospective cohort studies and clinical trials have demonstrated that regular physical exercise, especially aerobic exercise, significantly decreases the incidences of inflammation-related cancer types and the mortality of all cancer types via dose-dependently decreasing systemic chronic inflammation. The effect of aerobic exercise at the middle level intensity for 117–600 min per week on the survival of cancer patients can be more effective than that of the most advanced therapeutic technologies. The mechanisms by which long-term, regular physical exercise prevents cancer should be as follows: 1) decreases immunosenescence-induced low-grade, systemic chronic inflammation via increasing oxygen supply and remodeling gut microbiota composition and function. 2) increases innate immunity, cellular immunity, and humoral immunity via accelerating the process of metabolism and the turnover rate of immune cells. Encouraging public physical exercise and other healthy lifestyles decreasing systemic low-grade inflammation are the most cost-effective public health actions against cancer.