Currently, the demand of the human population for more land, water, and other natural resources from wildlife habitats is increasing all over the world. Such intense human pressure results in conflict with wildlife and the impacts affect both parties negatively. The human-hippo conflict poses a serious problem for both local farmers' livelihoods and hippo conservation. To date, the extent of human-hippo conflict is poorly documented in Ethiopia. Specifically, the extent of human-hippo conflicts around Lake Tana Biosphere Reserve (LTBR) is unknown. Therefore, this study aimed to investigate the extent of human-hippo conflict, and possible mitigation measures proposed by the local people around LTBR, Ethiopia. We conducted a questionnaire interview with the household head, the household head's wife, or other adults ≥ 18 years old. All respondents reported that crop damage was the main cause of human-hippo conflict around LTBR. Livestock grazing competition (17.4%) and human attack (19.5%) were also sources of conflicts in the region. Respondents claimed that hippos destroyed crops including maize (Zea mays), teff (Eragrostis teff), finger millet (Eleusine coracana), and rice (Oryza sativa). Most (91.2%) respondents claimed that the severity of crop damage caused by hippos was high in the region. Most respondents (range 90 to 93%) complained about high crop damage suggesting that hippos be eliminated from the region. Local people estimated that the population sizes of hippos comprise an average of 243 individuals; however, we counted 122 hippos during our boat survey in the area. The result of this study showed that human-hippo conflicts cause negative effects on both farmers' livelihood and hippo conservation in the region. To mitigate human-hippo conflict, we suggest that proper land use zonation systems around key areas, broad awareness creation among local people, and alternative crop production should be promoted around the LTBR.