The determination of critical ventilation flow rate is significant for the risk control and the standard development during accidental hydrogen leakage in a confined space with hydrogen-related equipment. In this paper, an analytical model for calculating critical ventilation flow rate was proposed through the quantification and constraint solution of ventilation effect and ventilation cost. The experimental method was used to investigate the effects of nozzle diameter and stagnation pressure on diffusion and ventilation for horizontal hydrogen leakage in a cuboid chamber. Ventilations from 30m3/h to 180m3/h were carried out through the rectangular vent. It was shown that the peak concentration of the measuring point is positively correlated with the stagnation pressure and the nozzle diameter. The experimental data are used to verify the analytical model by calculating the effective ventilation time. The study demonstrates that the critical ventilation flow rate can be increased significantly at higher stagnation pressures and larger nozzle diameters. And the discrepancy of critical ventilation flow rates under different nozzle diameters will be enhanced with the increase of stagnation pressure. For the stagnation pressure of 0.4MPa, the critical ventilation flow rate under 4mm nozzle even increases by 52% relative to the 2mm nozzle.