The strong flow field in a hoistway will cause a significant piston effect during the operation of high-speed/ultra-high-speed elevator. Thus, studying the airflow in the hoistway and the reasonable opening of ventilation holes is important. First, a three-dimensional geometric model of the ventilation holes (VHs) and elevator car was established. Based on this model, a multi-region dynamic layering method was proposed. The movement of the unsteady airflow in hoistways with different numbers of VHs and the interaction between the VHs were then analyzed. The correctness of the numerical simulation method was verified by comparing the results of the simulation, experiments and theoretical calculations. Finally, the influence of the number, location and cross-sectional area of the VHs on the airflow movement was analyzed, and the optimal opening positions of one and two pairs of VHs were discussed. The results showed that the variations of the number, location and cross-sectional area of the VHs had a significant influence on the airflow movement. According to the quantitative analysis of the ventilation efficiency, the optimal positions of one and two pairs of VHs were located in the middle of the hoistway and the upper and lower sides of the middle position, respectively.