The post-salt Itajai-Acu Formation of Cenomanian-Turonian developed a set of thick marine shale of predelta facies in Santos Basin. The source rocks of the shale are in immature to mature stage, and there exist overpressure in the shale and surrounding rocks. Drilling test pressure data and logging data were applied to analysis the causes of abnormal pressure, and to study the regularities of abnormal pressure and hydrocarbon migration. The overpressure in the northern part of southwestern shelf area of Santos Basin was caused by diagenesis, whereas that in middle-south part is caused by hydrocarbon generation. Hydrocarbon migration was driven by overpressure within range of overpressure on or under the overpressure layer, which benefited to form conventional and unconventional reservoirs. The lateral hydrocarbon migration distance was short. The vertical hydrocarbon migration distance is related to pressure difference, reservoir properties, and burial depth. Hydrocarbon migration was driven by buoyancy out range of overpressure on the overpressure layer, which benefited to form conventional oil and gas reservoir in the upper part on the overpressure layer, with fault as hydrocarbon migration channel. This recognition has expanded the exploration space and provided theoretical guidance for the exploration in the depression and slope areas of Santos Basin.