BACKGROUND Chronic non-communicable diseases have become the major cause of death in China. This study describes and compares chronic disease mortality between urban and rural residents in Hubei Province, central China. METHODS Death records of all individuals aged 15 years and over who died from 2008 through 2010 in Hubei were obtained from the Disease Surveillance Points system maintained by the Hubei Province Centers for Disease Control and Prevention. Average annual mortality, standardized death rates, years of potential life lost (YLL), average years of potential life lost (AYLL) and rates of life lost were calculated for urban and rural residents. Standardized rate ratios (SRR) were calculated to compare the death rates between urban and rural areas. RESULTS A total of 86.2% of deaths were attributed to chronic non-communicable diseases in Hubei. Cerebrovascular diseases, ischemic heart disease and neoplasms were the main leading causes in both urban and rural areas, and the mortality rates were higher among rural residents. Lung cancer was the principal cause of mortality from cancer among urban and rural residents, and stomach cancer and liver cancer were more common in rural than urban areas. Breast cancer mortality among women in rural areas was lower than in urban areas (SRR=0.73, 95% CI=0.63-0.85). The standardized mortality for chronic lower respiratory disease among men in rural areas was higher than in urban areas (SRR=4.05, 95% CI=3.82-4.29). Among men, total AYLL from liver cancer and other diseases of liver were remarkably higher than other causes in urban and rural areas. Among women the highest AYLL were due to breast cancer in both urban and rural areas. CONCLUSIONS Chronic diseases were the major cause of death in Hubei Province. While circulatory system diseases were the leading causes in both urban and rural areas, our study highlights that attention should also be paid to breast cancer among women and chronic lower respiratory disease among rural residents. It is important that governments focus on this public health issue and develop preventive strategies to reduce morbidity and premature mortality from chronic non-communicable diseases.