In order to solve the seal failure and string safety problems caused by unreasonable application of prestress on the positioning seal of the injection pipe string in Q Oilfield of Bohai Sea, the wellbore string model of the injection well was established by using Landmark software to simulate and analyze the string expansion during the injection process of well X1 and the mechanical behavior changes of the pipe string after different prestress was applied to the positioning seal. The results show that the scientific application of positioning sealing prestress according to different well inclines can reduce the risk of pipe seal failure. The research results can provide theoretical support for the rational application of positioning sealing prestress to the waterflood string in Q oilfield.