What is already known on this topic? Hemorrhagic fever with renal syndrome (HFRS) is endemic in Liaoning Province. Both Seoul and Hantaan virus are circulating in rodents, and epidemic outbreaks and sporadic cases have been recorded every year since the disease was recognized. What is added by this report? The epidemic trend of HFRS over the past 20 years (1999-2018) in Liaoning was analyzed, which showed both regional complexity and consistence with the epidemic in China. Genetic and antigenic stability of the circulating hantavirus were demonstrated, which suggested the effectiveness of the approved inactivated vaccine currently used in China. What are the implications for public health practice? Precise risk-based strategic practices that are integrated and regional are required for further improvement of the prevention and control of HFRS.