During the operation of ultra-deep wells, the sudden change of annulus pressure caused by the start-up of expansion tube is often misjudged as a leak in the string, which interrupts the construction and affects the progress of the operation and the measure efficacy. To address this problem, firstly, the coupling effects of expansion tube volume, annular fluid volume, string deformation, and annular pressure are considered comprehensively. Then, based on the operating principle of expansion tube and the state analysis of the expansion tube start-up, a transient prediction model of annular pressure at the expansion tube start-up was established by combining with PVT state equation. After studying the influencing factors and predicting the transient annulus pressure of an ultra-deep well with acid pressure test, we concluded that:1)The result of prediction model meets the field production requirements with a relative error of only 1.4%;2)The main factors affecting transient change of annulus pressure are compressibility of the annular fluid and volume change of the expansion tube. The elastic modulus of oil casing has little effect. This paper provides guidance for field constructor to address misjudgment caused by sudden changes of annulus pressure during the start-up of expansion tube.