Based on the characteristic analysis of Isopropanol-Isopentanol-Methyl-cyclohexane azeotrope system, the azeotrope separation process was established in combination with the actual working condition of the treated feed liquid. Under the condition of ensuring separation requirements, the main parameters of  each tower were determined by single factor optimization using the sensitivity analysis based on the principle of minimum annual total cost. On this basis, the process parameters of T0101 were further optimized by using orthogonal design. The results show that the optimal process parameters under the experimental control index of isopentanol mass fraction are as follows: the number of theoretical stage is 32, the feed position is the 10th stage, and the reflux ratio is 0.9. Under these conditions, the isopentanol mass fraction is 0.9981, which meet the requirements of product separation process.