Background The mortality of humans due to rabies in China has been declining in recent years, but it is still a significant public health problem. According to the global framework, China strives to achieve the goal of eliminating human rabies before 2030. Methods We reviewed the epidemiology of human deaths from rabies in mainland China from 2004 to 2018. We identified high risk regions, age and occupational groups, and used a continuous deterministic susceptibility-exposure-infection-recovery (SEIR) model with periodic transmission rate to explore seasonal rabies prevalence in different human populations. The SEIR model was used to simulate the data of human deaths from rabies reported by the Chinese Center for Disease Control and Prevention (China CDC). We calculated the relative transmission intensity of rabies from canines to different human groups, and they provided a reliable epidemiological basis for further control and prevention of human rabies. Results Results showed that human deaths from rabies exhibited regional differences and seasonal characteristics in mainland China. The annual human death from rabies in different regions, age groups and occupational groups decreased steadily across time. Nevertheless, the decreasing rates and the calculated R.sub.0 s of canines of various human groups were different. The transmission intensity of rabies from canines to human populations was the highest in the central regions of China, in people over 45 years old, and in farmers. Conclusions Although the annual cases of human deaths from rabies have decreased steadily since 2007, the proportion of human deaths from rabies varies with region, age, gender, and occupation. Further enhancement of public awareness and immunization status in high-risk population groups and blocking the transmission routes of rabies from canines to humans are necessary. The concept of One Health should be abided and human, animal, and environmental health should be considered simultaneously to achieve the goal of eradicating human rabies before 2030.