When the vehicle is driving at high speed on a slippery road, the sideslip stiffness of the tire which is closely related to the lateral force of the tire, will vary with the change of road conditions, tire inflation pressure, vertical load, and other factors. If the tire sideslip stiffness is set to a fixed value in the control system based on the model design, the uncertainty of the sideslip stiffness will cause a large error with the actual application. Therefore, in order to improve the trajectory tracking accuracy of the vehicle on the slippery road surface under the premise of ensuring the stability of the vehicle, an intelligent vehicle trajectory tracking control strategy considering the influence of sideslip stiffness is designed in this paper. In order to solve the multiple constraints of the vehicle driving on the low-adhesion road surface, a trajectory tracking controller based on the multi-constraint model predictive control algorithm is designed, and then the tire sideslip stiffness estimation strategy is designed based on the XGBoost algorithm, and the estimated sideslip deviation stiffness is added to the trajectory tracking control model. Carsim and MATLAB/Simulink are used to perform co-simulation to verify the accuracy of the proposed tire sideslip stiffness estimation and the tracking performance of the trajectory tracking controller. In order to further verify the reliability of the research content, the relevant working condition tests are carried out on the hardware-in-the-loop platform based on Carsim and LabVIEW, and the effectiveness of the trajectory tracking controller considering the influence of sideslip stiffness is verified.