Haemorrhagic fever with renal syndrome (HFRS), a rodent-borne disease, is a major public health concern in both developed and developing countries. China is the most severe endemic country in the world, constituting 90% of the cases. Although the incidence of HFRS has substantively decreased in most areas of China, HFRS has rebounded remarkably in some epidemic areas. Xuancheng is one of these areas. In this study, we collected the case data reported recently in Xuancheng and designed a 1:3 case−control study. The Chi-square test, univariate and multivariate logistic regression analysis were performed. In all cases, farmers made up the highest proportion of occupations. And there were 20 variables with statistical significance including indoor hygienic conditions; the surrounding environment; whether bitten by rats at work and other criteria. In addition, exposure to rodents and rats bites is a high-risk factor for HFRS. Rodent density was calculated at 20.9% (159/760), the virus carrier rate was 9.4% (15/159) and the index of rats with a virus was about 2.0%. Exposure to rodents and insect bites is also high-risk factors for HFRS among local residents in Xuancheng. More importantly, during the flood years, the increased density of rodents led to an increased risk of human exposure to rodents. As our statistical analysis proves, targeted strategies should be developed and implemented to reduce the incidence of local diseases in the future.