Objective:To analyze the epidemic characteristics and spatio-temporal distribution of hemorrhagic fever with renal syndrome (HFRS) in Guangzhou from 2010 to 2019 and provide a basis for prevention and control strategies.Methods:The data of HFRS was from National Disease Reporting Information System and the epidemic investigation. A descriptive analysis was used. OpenGeoDa 1.2.0 software was used for global spatial autocorrelation and local spatial autocorrelation analysis. SatScan 9.6 software was used for detecting the hot spot area in time and space. ArcGIS 10.2 software was used for map visualization.Results:1 298 cases of HFRS were reported, and three patients died in Guangzhou in 2010-2019. The annual incidence rate was 0.99/100 000. The proportion of 21-50 years old cases accounted for 70.88% and the male to female ratio was 2.98∶1. Most patients were house workers or unemployed, accounting for 31.28%, followed by business servants (accounting for 17.33%). The incidence peak in spring and winter accounted for 33.74% and 26.35% of the year. All districts reported cases in recent ten years. A total of 407 cases had been reported in Haizhu district, accounting for 31.36% of the total number of cases in the whole city. The annual incidence rate was 2.52/100 000. The number of reported cases and the annual incidence rate were the highest in Guangzhou. The clustered area showed that there was spatio-temporal clustering in Guangzhou. The aggregation area was mainly concentrated in the urban villages adjacent to Wan-mu orchard and the Haizhu Lake Wetland Park in Haizhu district (logarithmic likelihood ratio was 44.08, P<0.001). Conclusions:The prevalence and concentration of HFRS in winter and spring Guangzhou city from 2010 to 2019, showed a high incidence. Young and middle-aged men engaged in domestic and unemployed, and commercial services appeared the main risk groups. The urban-rural junction with many immigrants and low health environment, streets adjacent to Wan-mu orchard, and the Haizhu Lake Wetland Park in Haizhu district were the important regions for preventing and controlling HFRS. The government should formulate prevention and control measures to curb the rise and spread of the HFRS epidemic.