Hepatitis E virus (HEV) infection in developing countries is associated with poor hygiene, lack of clean drinking water, and inadequate sanitation. In this study, we report the first case investigation and describe the present situation of HEV outbreak within displaced persons camps in the Diffa region, Republic of Niger. The investigation showed the outbreak to be closely linked to unclean water supply, low hygiene, and sanitation facility standards. Between January and September 2017, a total of 1,917 HEV suspect cases were recorded from which 736 (38.4%) have been confirmed positive for HEV by reverse transcription polymerase chain reaction and enzyme linked immunosorbent assay. Overall, 38 (1.9%) deaths were recorded, including 17 (44.7%) pregnant women. The ongoing outbreak highlights poor drinking water quality and sanitation conditions in displaced persons camps in the Diffa region. Disease containment and patient care activities, particularly for pregnant women, may have resulted in decreased transmission of infection and deaths.