The incidence and mortality rates of liver and nasopharyngeal cancer in Guangxi province of China have always been among the highest in the world, and cancer is one of the major diseases that pose a threat to the health of residents in Guangxi. However, no systematic study has been performed to evaluate the time trends in the structure of cancer-related deaths and cancer mortality. In this study, we reveal sex, age and geography differences of cancers mortality between three death surveys (1971 to 1973, 1990 to 1992, and 2004 to 2005). The results show that the standardized mortality rate of cancer in Guangxi residents has risen from 43.3/100,000 to 84.2/100,000, the share of cancer deaths in all-cause deaths has increased from 13.3% to 20.7%, and cancer has become the second most common cause of death. The five major cancers, liver cancer, lung cancer, gastric cancer, nasopharyngeal cancer and colorectal cancer, account for 60% of all the cancer deaths. Cancers with growing mortality rates over the past 30 years include lung cancer, colorectal cancer, liver cancer and female breast cancer, of which lung cancer is associated with the sharpest rise in mortality, with a more than 600% rise in both men and women. Cancer death in Guangxi residents occurs mainly in the elderly population above 45 years of age, especially in people over the age of 65. The areas with the highest mortality rates for liver cancer and nasopharyngeal cancer, which feature regional high incidences, include Chongzuo and Wuzhou. Therefore, for major cancers such as liver cancer, lung cancer, gastric cancer, nasopharyngeal cancer and female breast cancer in Guangxi, we can select high-risk age groups as the target population for cancer prevention and control efforts in high-prevalence areas in a bid to achieve the ultimate goal of lowering cancer mortality in Guangxi.