The multi-zone model is widely used to predict airflow and contaminant transport in large buildings under natural or mechanical ventilation. Selecting appropriate mixing factors and particle deposition velocities for the multi-zone model can compensate for the errors resulting from the model’s well-mixing assumption. However, different room types, air change rates and ventilation modes can result in different mixing factors and particle deposition velocities. This study selected three typical room types: Z-type, L-type, and rectangle type (R-type). For each room type, the mixing factors and particle deposition velocities were investigated by the CFD model under different natural ventilation rates (0.5 h?1, 1 h?1, 3 h?1, 6 h?1, 12 h?1 and 20 h?1) and modes (door-inlet, window-inlet). The results showed that the mixing factor of the Z-type room was the highest, and the mixing factors of these rooms were 1.32, 1.28 and 1.13, respectively. In addition, the mixing factors presented a V-shaped distribution as a function of the air exchange rate under the window-inlet mode. The particle deposition velocity increased as the air change rate increased, and also demonstrated that the V-shaped curves as a function of particle size (0.05 μm, 0.1 μm, 0.5 μm, 1 μm, 2.5 μm, 5 μm) varied under different air change rates and room types. The results of mixing factors and particle deposition velocities for different room types, air change rates and ventilation modes can be used to improve the accuracy of the multi-zone model.