The drainage pressure difference of self-cleaning screen filter was calculated, and the total value of pressure difference for 80 mesh and 120 mesh was also calculated respectively at first. Contrasting with measured value, the result indicated that the calculated value and measured value were substantial identical. Then, the law of pressure difference was analyzed particularly, which influenced by restriction condition as flow, sand and time, etc. Finally, the variation curve of clean and muddy head loss acquired by the experiments, under the condition that the head loss could not ascend sharply, the best drainage pressure difference for two kinds of mesh was put forward, which could provide reference for the pressure difference calculation of screen filter.