Wadi El-Assiuti Protected Area (WAPA) in Assiut Governorate is considered as the first and foremost zone for wildlife breeding and endangered species. This study investigates the effects of different environmental issues of both anthropogenic and natural factors on the wildlife of WAPA. The examined factors are air quality, water quality, noise levels, local weather, and human activity in WAPA. Additional to environmental agents, biodiversity is monitored by recording the number of each fauna type from 2008 to 2016. The results showed that several kinds of wildlife in WAPA have been endangered while numbers of other increased. The examined air, water, and local weather proved that they have no negative effects on the endangered species. The main reason of the disappeared or increases some species are the human activities especially cultivation and construction of several quarries in the WAPA zone. The quarries are companion with noise, dust, contaminations from their vehicles, and huge movement of human and trucks that have direct impact on the wildlife in WAPA. The main conclusion of this study is that removing the encroachment from the WAPA is the only method to protect its biodiversity.