For the threshold pressure gradient and the medium deformation characteristic in low permeability deformed medium sandstone reservoirs, an unsteady-state seepage model, which could predict the flood response time under different affecting factors more accurately, is established on the basis of the flow formula considering threshold pressure gradient and media deformation factor. The average formation pressure in the excited area has been solved by using repeated iteration method. And, the water flooding response calculation model in low permeability deformed medium sandstone reservoirs has also been established according to material balance method. The water flooding response is mainly affected by the well spacing, the average formation pressure in the excited region, the threshold pressure gradient and the media deformation factor. The flood response time sharply increases with the increase of well spacing or excited radius and the increase of water flooding response is getting faster with well spacing’s increment. The threshold pressure gradient or the media deformation factor greatly affects the water flooding response, and the greater the threshold pressure gradient or the media deformation factor, the longer the flood response time.