This paper introduces the stage difference equation (SDE) for distillation synthesis, which yields a series of liquid composition profiles for a plate tower. SDE is derived from mass balance through one common column section and identifies the relationship between two joined sections by its parameters. As these parameters need to be determined at first before applying SDE, their relations between composition and reflux ratio are then examined. SDE is used in nonreactive distillation and reactive distillation synthesis where the reactive stage difference equation (RSDE) is proposed based on reaction and variable transformations. Application case Studies to nonreactive and reactive distillations indicate that these equations can facilitate the determination of operating regime and conveniently produce optimal synthesis Solutions.