Abstract In this study, fluctuation with three frequencies is applied to the boundaries of the cyclone separator. Flow field including dominant frequency and amplitude of vortices at three regions (vortex finder, main cylinder, and cone) and performance parameters (collection efficiency and pressure drop) are studied. Lagrangian-Eulerian Frame is applied, and Large Eddy Simulation (LES) is used for turbulence modeling. Three inlet flows of 4, 6, and 8 [g/s] are considered. The Power Spectral Density (PSD) of fluctuations has been increased by increasing the inlet flow rate. The fluctuating flow will make vortices with higher amplitude than the uniform flow. Because the high amplitude vortex breaks into and transmits energy to the small vortex, pressure drop increases with frequency increment. The pressure drop equations in the non-uniform flow of the cyclone are derived based on the existing pressure drop relationships. The average separation efficiency in non-uniform flow is less than uniform flow.