Semi-trailer trucks, as the core transport vehicles in modern logistics systems, offer significant advantages in enhancing cargo turnover efficiency and reducing transportation costs. However, their high center of gravity, long body length, heavy load capacity, and strong coupling effects between the tractor and trailer result in poor high-speed stability. To address this issue, a control strategy combining a quantum particle swarm optimization (QPSO)-based model predictive control (MPC) with differential braking technology was proposed. Based on a three-degree-of-freedom vehicle model and Trucksim, a QPSO-MPC controller utilizing the QPSO algorithm was designed. Differential braking technology distributed braking force to individual wheels. Joint simulation using Trucksim and MATLAB/Simulink validated the control system’s effectiveness under high-speed single-lane, dual-lane, and slalom conditions. Research findings demonstrate that the designed controller effectively reduces the vehicle’s yaw rate and lateral acceleration under all three operating conditions, enhancing the high-speed stability of semi-trailer truck trains.