China is heavily affected by cancer. In 2022, the population in Chinese mainland accounted for 18.66% of the world, but new cancer cases and cancer-related deaths accounted for 24.17% and 26.44% of the world, respectively. Lung cancer, liver cancer, gastric cancer, colorectal cancer, and esophageal cancer are the top 5 histological types, accounting for 67.50% of all cancer-related deaths. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of liver cancer, gastric cancer, and esophageal cancer keep decreasing whereas their corresponding crude rates are increasing. The ASMR of lung cancer keeps decreasing in urban areas but increasing in rural areas. The ASIR and ASMR of colorectal cancer are increasing gradually. These data indicate that aging, movement of industrial pollution to rural areas, and alterations in lifestyle seriously affect cancer burden. Due to the rapid transformation of China’s economic, modern lifestyle-related risk factors including physical inactivity, smoking and alcohol consumption, metabolic syndrome, unhealthy diet, and psychological problems continue to increase; furthermore, poverty-related risk factors including environmental pollution, food contamination, and chronic infections (including the infections with hepatitis B virus, human papillomavirus, Helicobacter pylori, and Clonorchis sinensis) still exist, both pushing up the high burden of cancers in China at this stage. These causal factors are carcinogenic either by directly interfering genetic and epigenetic mechanisms, or most frequently induce chronic inflammation to inflammation-cancer transformation. Targeted interventions to the modifiable risk factors, such as improving lifestyle and increasing physical activity can reduce systemic inflammation and improve immunity, so as to decrease cancer occurrence and cancer-related death. In addition, cancer screening is helpful in decreasing the ASMRs of several slowly progressive cancer types including colorectal cancer. Epidemiological cohort study and experimental epidemiology are key to clarify the effects of primary prophylaxis, screening, and clinical treatments on the occurrence and prognosis of cancers, which is the key for improvement of cancer tertiary prophylaxis. Optimal combination of cancer prevention and clinical diagnosis and treatment should be an effective strategy to control the cancer-caused loss of life expectancy in a cost-effective way.