In-wheel motors are used in heavy vehicles such as buses and trucks to improve efficiency and compactness, the safety of which is particularly important. Anti-slip control is applied to road vehicles to improve the active safety performance, and it is necessary for heavy in-wheel motor vehicles. However, the experiment results in this study show that the response delay of motors on the heavy vehicle is larger than that of the passenger car, and the vehicle mass often changes, which brings drawbacks to the rapidity and stability of its dynamics control. For these problems, an improved Proportional-Derivative Control with a modifying desired wheel rotational speed is proposed for the slip regulation. The modifying control target is intended to mitigate steady tracking error, the role of which is similar to the traditional Integral Control. The desired wheel rotational speed is modified through the response in the current period, and then is set as the new target in the next period. Because the anti-slip control of driving wheels on each side is independent, the torque reallocation strategy is introduced to coordinate with the yaw control and take the yaw dynamics into account, which therefore improves the lateral stability. To avoid the excessive driving torque increment causing the slipping phenomenon again, after the anti-slip control finishing, a transition process is applied. Finally, simulations and real vehicle experiments are conducted to verify the effectiveness and flexibility of the control algorithm, and the results indicate that the control strategy has an expected performance.