This paper presents the optimization of a system of square cascades for separating the middle components of xenon. It also presents the optimal use of square cascades in this system. As an example, the separation of 130 Xe, an element whose middle isotope is much more complex than any of the other isotopes of xenon, is provided. The Grey Wolf Algorithm is applied for optimization. and the parameters of cascade feed flow rate, cut off the cascade, feed location, feed flow of gas centrifuges (GC), and the cut of the first stage are optimized in such a way that the maximum recovery of the target isotope and the maximum cascade capacity are achieved. Based on the optimization results, the more steps the cascade has, the fewer separation steps are needed for the nine selected cascades with 180 GCs. As a result, both the recovery factor and the amount of product increase.