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Background: Brucellosis is a major public health issue in China, while its temporal and spatial distribution have not been studied in depth. This study aims to better understand the epidemiology of brucellosis in the mainland of China, by investigating the human, temporal and spatial distribution and clustering characteristics of the disease., Methods: Human brucellosis data from the mainland of China between 2012 and 2016 were obtained from the China Information System for Disease Control and Prevention. The spatial autocorrelation analysis of ArcGIS10.6 and the spatial-temporal scanning analysis of SaTScan software were used to identify potential changes in the spatial and temporal distribution of human brucellosis in the mainland of China during the study period., Results: A total of 244 348 human brucellosis cases were reported during the study period of 2012-2016. The average incidence of human brucellosis was higher in the 40-65 age group. The temporal clustering analysis showed that the high incidence of brucellosis occurred between March and July. The spatial clustering analysis showed that the location of brucellosis clustering in the mainland of China remained relatively fixed, mainly concentrated in most parts of northern China. The results of the spatial-temporal clustering analysis showed that Heilongjiang represents a primary clustering area, and the Tibet, Shanxi and Hubei provinces represent three secondary clustering areas., Conclusions: Human brucellosis remains a widespread challenge, particularly in northern China. The clustering analysis highlights potential high-risk human groups, time frames and areas, which may require special plans and resources to monitor and control the disease.