A large number of road traffic accidents occur each year in China, which results in huge losses to the safety of people’s lives and property. Among all accidents, the accident with over 10 fatalities in one accident is extraordinarily serious, which has immeasurable impact on the security. In this paper, we defined these accidents as serious fatal road traffic accidents (SF-RTAs). The aim of this study was to analyze SF-RTAs in China and its provinces and investigate the causes of SF-RTAs. Firstly, we described and analyzed the annual trend of SF-RTAs based on the data from 1990 to 2014. Then we analyzed region, time and accident type distribution characteristics of SF-RTAs during 2004-2014. Then the main factors influencing SF-RTAs were analyzed by linear regression and decision tree methods. Finally, we proposed corresponding control strategies for preventing SF-RTAs according to the analysis results. It is expected that the findings of this study are useful in indentifying effective prevention measures for serious fatal accidents in China, and protecting human lives and properties.