In arid and semi-arid regions there are a large gap between water supply and water demand especially in Egypt. This gap can be covered by different techniques including modern irrigation system, rationalization of using freshwater, reuse of agricultural drainage water and wastewater. This study aims to investigate the effect of using untreated and treated wastewater in irrigation on groundwater quality using the finite difference model (MODFLOW). Two scenarios are studied, the first is using untreated wastewater in irrigation and the second is using treated wastewater due to reduction of freshwater by 10, 20, 30, 40 and 50 %. The results showed that using untreated wastewater in irrigation has significant effect in groundwater quality and loss large quantity of freshwater in the aquifer, while using treated wastewater in irrigation is more suitable for protecting groundwater. Also using untreated wastewater in irrigation under the reduction of irrigation water due to climate changes and construction of control structure on the upper Nile River must be considered to protect the groundwater and keeping the human health. The technology of treated wastewater should be extend in arid and semi-arid regions to overcome the shortage of water resource and increase the quality of drink and irrigation water from the groundwater.