This study aimed to estimate the disease burden of hepatitis E in a rural region in China. A total of 489 hepatitis E cases were reported according to a community-based survey in an active hepatitis surveillance system between 2008 and 2015, the questionnaire and record-review methods were constructed to evaluate the economic and health burden of hepatitis E virus infections from societal perspectives. All costs were converted to US$ in 2015. The age-standardized cumulative incidence rate was 107·9/100 000, and the median age-standardized annual incidence rate was 16·5/100 000. The median direct, indirect, and intangible cost were $1046·0, $49·1, and $77·3/patient, respectively, and the median economic burden per patient was $1836·5, which accounted for 51·2% of per capita disposable income. Moreover, the median quality-adjusted life year and visual analogue scale score were 0·7 and 70·0/case, respectively. Both economic burden and health burden of inpatients was more serious than that of outpatients (P < 0·001). Disease burden of hepatitis E is heavy on patients, their families, and society. More studies on the disease burden of hepatitis E are necessary to increase social awareness of the disease and confirm reasonable disease-control measures.