The purpose of this paper is to study the pressure drop of an axial flow cyclone separator as a function of inlet velocities using experimental and computational fluid dynamics (CFD) methods. First, the resistance performance of the separator was acquired under ambient pressure and temperature with little change by wind tunnel experiments. Then, numerical simulations were carried out in CFD code Fluent 6.3 under standard operating conditions. A comparison between the experimental and CFD data demonstrates that the CFD method can predict the pressure drop of the axial cyclone separator excellently. Additionally, the results show that the axial flow cyclone separators have a pressure drop coefficient of approximately 7.5. To study the effect of ambient pressure and temperature on pressure drops, the same CFD method was employed to predict the resistance performance under various operating conditions. Then the numerical results were compared with the data of a normalization process method of pressure drops raised in this paper. Their comparison demonstrated that the normalization method had a high precision in predicting the influence of ambient operating parameters on pressure drops of an axial flow cyclone separator.