Abstract: With population aging and the great improvement in life following economic development, the burden (incidence and mortality) of chronic diseases, particularly malignant tumors, is becoming heavier. Carcinogenesis and tumor progression typically arise from persistent inflammation, necrosis, and proliferation in targeted tissues and/or organs on the basis of systemic low-grade chronic inflammation. Factors facilitating this process are the risk factors of cancer. Large-scale prospective cohort studies have demonstrated that regular physical exercise, especially aerobic exercise, significantly decrease the incidence of inflammation-related cancer types and the mortality of all cancer types by attenuating systemic low-grade chronic inflammation, with a dose-dependent effect. The effect of aerobic exercise at the middle level intensity for 117‒600 min per week on the reduction of cancer mortality can be more effective than that of immunotherapy combinations (50% vs 26%). The mechanisms by which regular physical exercise prevents cancer may lie in the long-term, regular physical activity increasing oxygen supply and optimizing gut probiotics, thereby reducing systemic low-grade chronic inflammation caused by immunosenescence, promoting the renewal of immune cells to enhance levels of non-specific immunity, cellular immunity and humoral immunity. Encouraging public physical exercise and other healthy lifestyles including optimizing food components to decrease systemic low-grade chronic inflammation are the most cost-effective public health strategies against cancer.