The second generation biofuel butanol can be produced by acetone-butanol-ethanol (ABE) fermentation, but the separation from the broth is still challenging. Therefore, dipotassium hydrogen phosphate was investigated as salting-out agent. The ABE fermentation broth was enriched by a prefractionator after being preheated. The enriched ABE solution was salted out by K2HPO4 solutions at different temperatures. The water in the supplemented ABE solution was largely removed by the salting-out method. The energy requirements for the prefractionator and the butanol column were significantly reduced. The total energy demand for the recovery of acetone, butanol, and ethanol by salting-out and subsequent distillation was optimized. With the salting-out process, the entire salting-out and distillation method turned out to be more energy-saving than the conventional one.