Hepatitis E virus is a common hepatotropic virus that causes serious gastrointestinal symptoms. Data of reported HEV cases in Zhejiang Province was collected between 2007 and 2012. Descriptive epidemiological methods and spatial-temporal epidemiological methods were used to investigate the epidemiological trends and identify high-risk regions of hepatitis E infection. In this study, the average morbidity of hepatitis E infection was 4.03 per 100,000 in Zhejiang Province, peaking in winter and spring. The ratio between the male and the female was 2.39:1, and the high-risk population was found to be aged between 40 and 60. Trend surface analysis and IDW maps revealed higher incidences in the northwestern counties. The spatial-temporal analysis showed comparable incidences in the counties at the basins of three rivers, mostly under administration of Hangzhou Municipality. Besides, the seasonal exponential smoothing method was determined as the better model for the retrieved data. The epidemiological characteristics of HEV suggested the need of strengthened supervision and surveillance of sanitary water, sewage treatment and food in high-risk areas especially around the Spring Festival. Additionally, time series model could be useful for forecasting the epidemics of HEV in future. All these findings may contribute to the prevention and control of HEV epidemics.