The separation process of synthesizing MIBK (methyl isobutyl ketone) by an isopropanol one-step method,in which the multi-component mixture contains AC (acetone), IPA (isopropanol), water, MIBK, MIBC (methyl isobutylcarbinol), DIBK (di-isobutyl ketone), etc., was studied. As a high-purity of MIBK over 99.5wt% is required in industry,the development of an effective separation method is urgent. In this work, first, by means of VLE (vapor-liquid equi-librium) experiments and PROII simulation, the possible azeotropes formed in the investigated system were tested.Then, the separation process was simulated with the result that the calculated and designed values were in good agree-ment, which indicated that the calculated results were reliable. On this basis, the original separation process was im-proved. In the original separation process, the yield of MIBK for a concentration of MIBK over 99.5wt% was small,only 32.5%. In the improved separation process (step two), two columns (one extractive distillation column and theother solvent recovery column) were added and some simplification was made so as to recycle MIBK. In this case theyield of MIBK was 91.7%. Moreover, about 27.6% water stream per kilogram MIBK product is saved.