The production of an offshore oil and gas production system has the extreme flow pattern of slug flow. Its gas volume fraction (GVF) still has strong fluctuation after buffering by a homogenizer. The abnormal vibration of the multiphase pump is caused by the fluctuating incoming flow, which challenges the stable operation and life of the pump. In this paper, the transient fluid–structure interaction method is used to study the force and deformation of a three-stage multiphase pump under fluctuating flow. The results show that the circumferential force is unbalanced and fluctuates greatly under the influence of fluctuating incoming flow. Its main frequency characteristics change from blade frequency to GVF fluctuation frequency, and there is still a lot of noise frequency after the radial force is stabilized. Under the influence of flow pattern change, the static pressure and load distribution of the blades of the second- and third-stage impellers are obviously separated. The maximum load position of the blade is transferred from the rear half to 0.4 times the relative position. The maximum deformation occurs at the tip of the blade, and the influence of the fluctuating flow on it decreases step by step.