In this work, we attempted to simulate UF6 gas flow in the rarefied and continuum areas of the rotating cylinder using CFD, DSMC, and hybrid one-way and two-way CFD-DSMC methods. In the hybrid two-way CFD-DSMC method, the effect of two rarefied and continuum areas on each other is considered. The results were verified by the DSMC method. The results presented the two-way CFD-DSMC method was useful for three goals. The first purpose was to simulate the flow in the rarefied area using the DSMC method, which was more valid than the CFD method. The second goal was to reduce the computational time of the simulation of the continuum area using the CFD method. The third goal was to investigate the effect of the rarefied solution on the continuum solution. Comparing the results with the DSMC method, it was found that the two-way CFD-DSMC method causes a difference of only 2% for the separation power, while the computational cost is reduced by 60%.