Background: To summarize and compare the difference in cancer incidence and mortality between China and the United States (US). Methods: Incidence and mortality data were extracted from the GLOBOCAN2020. US data were obtained from the American Cancer Society, while China’s data were obtained from 92 cancer registries in rural and urban settings. Age-standardized incidence or mortality rates were presented based on the World Standard Population which was proposed by Segi (1960). Incidence rate ratio and mortality rate ratio were calculated to compare the difference between the two countries. Results: In 2020, there are 4.6 and 2.3 million new cases in China and the US, respectively. The age-standardized incidence rates of all cancers in China and the US are 174.0 per 100,000 and 318.0 per 100,000, respectively. The incidence rate ratio of all cancer China to the US is 0.57, while the mortality rate ratio is 1.50. The age-standardized incidence rates of melanoma, prostate cancer, and Hodgkin’s lymphoma in the US are 46.1, 7.1, and 5.4 times greater than in China, respectively. While the age-standardized incidence rates of nasopharynx cancer, esophagus cancer, and stomach cancer in China are 7.5, 4.9 and 4.9 times that of the US, respectively. The age-standardized mortality rates of nasopharynx cancer, oesophagus cancer and stomach cancer are 10.0, 5.3, and 9.4 times that of the US, respectively. The age-standardized mortality rates of oropharynx cancer, testis cancer, corpus uteri cancer, vulva cancer, mesothelioma, multiple myeloma, and melanoma of skin in the US are 2.5 to 6.1 times greater than in China. Conclusions: There are big differences in the cancer spectrum between the two countries. Factors of economy, environment, diet, and living habits are the possible reasons for such differences. While facing increasing tumor burden challenge, improving residents’ awareness of risk factors, recognizing genetic risk, and strengthening early screening are feasible options to be implemented.