摘要Objective The Guanzhong Plain of Shaanxi Province is a severely afflicted hemorrhagic fever with renal syndrome (HFRS) epidemic area, while HFRS prevalence has decreased in most epidemic areas in China. Little information is available regarding the leading fine-scale influencing factors in this highly HFRS-concentrated area and the roles of natural environmental and socioeconomic factors. To investigate this, two regions in the Guanzhong Plain, that is, the Chang'an District and Hu County, with similar geographical environments, different levels of economic development, and high epidemic prevalence, were chosen as representative areas of the HFRS epidemic. Methods Maximum entropy models were constructed based on HFRS cases and fine-scale influencing factors, including meteorological, natural environmental, and socioeconomic factors, from 2014 to 2016. Results More than 95％ of the HFRS cases in the study area were located in the northern plains, which has an altitude of less than 800 m, with topography contributed 84.1％ of the impact on the spatial differentiation of the HFRS epidemic. In the northern plains, precipitation and population density jointly affected the spatial differentiation of the HFRS epidemic, with contribution rates of 60.7％ and 28.0％, respectively. By comparing the influencing factors of the northern plains of Chang'an District and Hu County, we found that precipitation and the normalized difference vegetation index (NDVI) dominated the HFRS epidemic in the relatively developed Chang'an District, while land-use type, temperature, precipitation and population density dominated the HFRS epidemic in the relatively undeveloped Hu County. Conclusion Topography was the primary key factor for HFRS prevalence in the Chang'an District and Hu County, and the spatial differentiation of HFRS was dominated by precipitation and population density in the northern plains. Compared with the influencing factors of the relatively developed Chang'an District, the developing Hu County was more affected by socioeconomic factors. When formulating targeted HFRS epidemic prevention and control strategies in the targeted areas, it is crucial to consider the local economic development state and combine natural environmental factors, including the meteorological environment and vegetation coverage.