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Background: Typhoid fever and paratyphoid fever are one of the most criticial public health issues worldwide, especially in developing countries. The incidence of this disease may be closely related to socio-economic factors, but there is a lack of research on the spatial level of relevant determinants of typhoid fever and paratyphoid fever. Methods: In this study, we took Hunan Province in central China as an example and collected the data on typhoid and paratyphoid incidence and socio-economic factors in 2015–2019. Firstly spatial mapping was made on the disease prevalence, and again using geographical probe model to explore the critical influencing factors of typhoid and paratyphoid, finally employing MGWR model to analysis the spatial heterogeneity of these factors. Results: The results showed that the incidence of typhoid and paratyphoid fever was seasonal and periodic and frequently occurred in summer. In the case of total typhoid and paratyphoid fever, Yongzhou was the most popular, followed by Xiangxi Tujia and Miao Autonomous Prefecture, Huaihua and Chenzhou generally focused on the south and west. And Yueyang, Changde and Loudi had a slight increase trend year by year from 2015 to 2019. Moreover, the significant effects on the incidence of typhoid and paratyphoid fever from strong to weak were as follows: gender ratio(q = 0.4589), students in ordinary institutions of higher learning(q = 0.2040), per capita disposable income of all residents(q = 0.1777), number of foreign tourists received(q = 0.1697), per capita GDP(q = 0.1589), and the P values for these factors were less than 0.001. According to the MGWR model, gender ratio, per capita disposable income of all residents and Number of foreign tourists received had a positive effect on the incidence of typhoid and paratyphoid fever. In contrast, students in ordinary institutions of higher learning had a negative impact, and per capita GDP shows a bipolar change. Conclusions: The incidence of typhoid and paratyphoid fever in Hunan Province from 2015 to 2019 was a marked seasonality, concentrated in the south and west of Hunan Province. Attention should be paid to the prevention and control of critical periods and concentrated areas. Different socio-economic factors may show other directions and degrees of action in other prefecture-level cities. To summarize, health education, entry-exit epidemic prevention and control can be strengthened. This study may be beneficial to carry out targeted, hierarchical and focused prevention and control of typhoid fever and paratyphoid fever, and provide scientific reference for related theoretical research. [ABSTRACT FROM AUTHOR]