Abstract: In order to deal with the problem of lacking quantitative analysis about the effect of sedimentary conditions and burial process on layers overpressure in deep zones, the geology models of different sedimentary conditions and different burial progress has been established in this paper. And then, the numerical simulation about the overpressure distribution of different lithology layers on the conditions of different lithological associations, different thicknesses of overlying cap rock, different burial ways and different sedimentary velocities have been used to quantitatively analyze and summary the effect of sedimentary conditions and burial process on layers overpressure in deep zones. The results show that the overpressure magnitude in the layers become bigger with the increase of sedimentary velocity and overlying cap rock depth, and this increase effect in the mudstones are higher than that in the sandstones. The overpressure magnitude in the layers also become bigger as the mudstone content in the layer becomes bigger, and the increase effect of overpressure in the layers due to the increase of mudstone content in the layer are more obvious than that caused by the increase of sedimentary velocity and overlying cap rock depth. The changes of burial way can cause the change of overpressure in the deep layers, and this changing rule is not necessarily consistent between sandstone and mudstone or between the mudstones of different depths, which relates with the superimposed effect of multi-factors, having different effect rules on the overpressure in the layer under the conditions of different burial ways. This study may supply the important evidence for deepening the understanding of genetic mechanism of overpressure in the deep zones.