Abstract: Objective To analyze the main causes of death and the potential years of life lost (PYLL) among residents in Guangzhou in 2011. Methods The population data in 2011 were provided by the Health Bureau of Guangzhou City. The data of death causes of Guangzhou in 2011 were obtained from the registry and report system of death causes. The causes of death were classified according to ICD-10. The leading causes of death and the potential life loss among residents in Guangzhou in 2011 were evaluated by the mortality rate, life expectancy, cause-deleted life expectancy and PYLL. Results There were 44262 cases of deaths in Guangzhou in 2011. The mortality rate was 544.47/100000 (standardized rate was 336.45/100000) in 2011.The mortality rates were 612.50/100000 (standardized rate was 431.12/100000) in male and 474.66/100000 (standardized rate was 248.26/100000) in female. The mortality in male was significantly higher than that in female (P<0.01). The six leading causes of death were malignant neoplasms, heart diseases, respiratory diseases, cerebrovascular diseases, acatalepsy, and injury, and their death rates were 133.44/100000, 101.82/100000, 100.68/100000, 73.70/100000, 31.54/100000, and 26.53/100000, respectively. The life expectancy was 80.83 years. It would increase 3.81, 2.78, and 2.73 years if removing the three leading causes of death. Their PYLL were 107716.00, 81414.00, 81106.50, 61978.50, 26523.00, and 22232.50 years. Conclusion The chronic diseases, especially, extraordinary malignant neoplasms, heart diseases, and respiratory diseases were the main causes of deaths in Guangzhou in 2011. The prevention and treatment of malignant neoplasms, heart diseases, respiratory diseases should be the focus of healthcare in Guangzhou. In particular, the prevention of tumorigenesis and the early diagnosis and treatment are crucial to the reduction of population life lost.