© 2017, Cheng et al. Background: Traumatic brain injury (TBI) is a significant global public health problem, but has received minimal attention from researchers and policy-makers in low- and middle-income countries (LMICs). Epidemiological evidence of TBI morbidity and mortality is absent at the national level for most LMICs, including China. Using data from China’s Disease Surveillance Points (DSPs) system, we conducted a population-based longitudinal analysis to examine TBI mortality, and mortality differences by sex, age group, location (urban/rural), and external cause of injury, from 1 January 2006 to 31 December 2013 in China. Method and findings: Mortality data came from the national DSPs system of China, which has coded deaths using the International Classification of Diseases–10th Revision (ICD-10) since 2004. Crude and age-standardized mortality with 95% CIs were estimated using the census population in 2010 as a reference population. The Cochran–Armitage trend test was used to examine the significance of trends in mortality from 2006 to 2013. Negative binomial models were used to examine the associations of TBI mortality with location, sex, and age group. Subgroup analysis was performed by external cause of TBI. We found the following: (1) Age-adjusted TBI mortality increased from 13.23 per 100,000 population in 2006 to 17.06 per 100,000 population in 2008 and then began to fall slightly. In 2013, age-adjusted TBI mortality was 12.99 per 100,000 population (SE = 0.13). (2) Compared to females and urban residents, males and rural residents had higher TBI mortality risk, with adjusted mortality rate ratios of 2.57 and 1.71, respectively. TBI mortality increased substantially with older age. (3) Motor vehicle crashes and falls were the 2 leading causes of TBI mortality between 2006 and 2013. TBI deaths from motor vehicle crashes in children aged 0–14 years and adults aged 65 years and older were most often in pedestrians, and motorcyclists were the first or second leading category of road user for the other age groups. (4) TBI mortality attributed to motor vehicle crashes increased for pedestrians and motorcyclists in all 7 age groups from 2006 to 2013. Our analysis was limited by the availability and quality of data in the DSPs dataset, including lack of injury-related socio-economic factors, policy factors, and individual and behavioral factors. The dataset also may be incomplete in TBI death recording or contain misclassification of mortality data. Conclusions: TBI constitutes a serious public health threat in China. Further studies should explore the reasons for the particularly high risk of TBI mortality among particular populations, as well as the reasons for recent increases in certain subgroups, and should develop solutions to address these challenges. Interventions proven to work in other cultures should be introduced and implemented nationwide. Examples of these in the domain of motor vehicle crashes include policy change and enforcement of laws concerning helmet use for motorcyclists and bicyclists, car seat and booster seat use for child motor vehicle passengers, speed limit and drunk driving laws, and alcohol ignition interlock use. Examples to prevent falls, especially among elderly individuals, include exercise programs, home modification to reduce fall risk, and multifaceted interventions to prevent falls in all age groups.