Hemorrhagic fever with renal syndrome (HFRS) is one of the 10 major infectious diseases that jeopardize human health and is distributed in more than 30 countries around the world. China is the country with the highest number of reported HFRS cases worldwide, accounting for 90% of global cases. The incidence level of HFRS in Quzhou is at the forefront of Zhejiang Province, and there is no specific treatment for it yet. Therefore, it is crucial to grasp the epidemiological characteristics of HFRS in Quzhou and establish a prediction model for HFRS to lay the foundation for early warning of HFRS. Descriptive epidemiological methods were used to analyze the epidemic characteristics of HFRS, the incidence map was drawn by ArcGIS software, the Seasonal AutoRegressive Integrated Moving Average (SARIMA) and Prophet model were established by R software. Then, root mean square error (RMSE) and mean absolute error (MAE) were used to evaluate the fitting and prediction performances of the model. A total of 843 HFRS cases were reported in Quzhou City from 2005 to 2022, with the highest annual incidence rate in 2007 (3.93/100,000) and the lowest in 2022 (1.05/100,000) (P trend<0.001). The incidence is distributed in a seasonal double-peak distribution, with the first peak from October to January and the second peak from May to July. The incidence rate in males (2.87/100,000) was significantly higher than in females (1.32/100,000). Farmers had the highest number of cases, accounting for 79.95% of the total number of cases. The incidence is high in the northwest of Quzhou City, with cases concentrated on cultivated land and artificial land. The RMSE and MAE values of the Prophet model are smaller than those of the SARIMA (1,0,1) (2,1,0)12 model. From 2005 to 2022, the incidence of HFRS in Quzhou City showed an overall downward trend, but the epidemic in high-incidence areas was still serious. In the future, the dynamics of HFRS outbreaks and host animal surveillance should be continuously strengthened in combination with the Prophet model. During the peak season, HFRS vaccination and health education are promoted with farmers as the key groups.