Xi’an, the capital of Shaanxi province, located in north-west China, is one of the major endemic areas for haemorrhagic fever with renal syndrome (HFRS). In this study, the epidemiological data of HFRS in Xi’an from 1959 to 2010, especially in the past ten years (2001–2010), were surveyed. The features of hantavirus (HV) host carriers, the molecular characteristics of the HV S gene from hosts and patients, and the genome of the viral isolate were also investigated. Data showed that there might be a ten-year cycle of HFRS in Xi’an. Although the main population group infected over the past ten years was still the 16–59-year-old male farmers, the composition of the population and geographical distribution of HFRS cases have changed slowly, accompanied by the development of environmental and socio-economic situations. Apodemus agrarius remains the dominant host of HV. The HV strains from host rodents and patients in Xi’an belonged to the Hantaan virus (HTNV); no Seoul virus strains were found. Phylogenetic analysis of the small segments of strains taken from hosts and patients, and the whole genome of a viral isolate showed that the virus circulating in Xi’an had high similarity to Guizhou strains. The study also indicated that the vaccine candidate strain A16 isolated during the past century in Xi’an might be a recombinant strain of HTNV and the Amur virus, thus it may not be an optimal vaccine strain.