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In recent years, hemorrhagic fever with renal syndrome (HFRS) incidence has been becoming a severe public health problem again due to its significant increase in Shaanxi Province, China. Baoji, located in the Guanzhong Plain in the central parts of Shaanxi Province, has been severely affected by HFRS since its first emergence in 1955. To better understand the epidemiology of orthohantaviruses infection in humans and the causative agents carried by the rodents, the long-term incidence patterns were analyzed and a molecular epidemiological investigation of orthohantaviruses infection in humans and rodents was performed. During 1984–2019, 13,042 HFRS cases were registered in Baoji, including 275 death cases. Except the first high prevalence of HFRS in 1988–1993, another two epidemic peaks were observed in 1998–2003 and 2012, respectively, although vaccination project was started since 1996. During the same period, HFRS cases in Baoji mainly were recorded in winter suggesting they may be caused by Hantaan orthohantavirus (HTNV), while a small peak of HFRS was also found in summer with unknown reason. Nucleotide identity and phylogenetic analyses demonstrated that a novel clade of HTNV sequences recovered from HFRS cases were closely related to those from rodents, including species close contact with humans, suggesting a direct viral transmission from rodents to humans and the important role in the HTNV transmission the nontraditional rodent hosts may play. Moreover, two distant related Dabieshan orthohantavirus (DBSV) lineages were also identified in Niviventer niviventer in this area demonstrating its considerable genetic diversity. Our data indicated that continual spillover of HTNV from rodents to humans, contributing to the high prevalence of HFRS in humans in Baoji. Author summary: Hemorrhagic fever with renal syndrome (HFRS) is a serious public health problem and affected Baoji in Shaanxi, China despite onset of free vaccination in populations. Hence, the epidemiology of HFRS was analyzed and a molecular investigation was performed in Baoji. During 1984–2019, a total of 13,042 HFRS cases were recorded and three epidemic peaks were observed. Moreover, 275 deaths were registered, with an average fatality rate of 2.10%. Phylogenetic analysis was indicative of directive transmission of Hantaan orthohantavirus (HTNV) from rodents, including nontraditional rodent hosts to humans because viral sequences obtained from patients in Baoji were very closely related to those from rodents. Our limited data indicated a continual spillover of HTNV from rodents to humans occurred in Baoji, responsible for the periodic high prevalence of HFRS, highlighting the need of continuous surveillance of HTNV in rodents and humans. In addition, two novel Dabieshan orthohantavirus (DBSV) lineages were also identified, suggesting its high genetic diversity. [ABSTRACT FROM AUTHOR]