The methanol-chlorobenzene mixture has a larger relative volatility in the low composition range than in the high composition range. Based on this characteristic, the mixture can be effectively separated by separate heat-pump distillation (SHPD) with significant energy savings. The binary interaction parameters of the UNIQUAC equation were used to predict the vapor-liquid equilibrium by means of the binary interaction parameters included in the Aspen Plus database. To minimize the overall annual operating costs, simulations for SHPD were carried out using Aspen Plus software, including the RadFrac and Compr blocks, and the optimal operating conditions, such as the split-point concentration, were determined. Simulations for conventional distillation, conventional heat-pump distillation, and multieffect distillation processes were also carried out for comparison. The simulated results showed that the SHPD process has obvious advantages over the other distillation processes in the assessment of energy savings and overall economic efficiency.