An optimization method for overlay error compensation is disclosed. The method comprises setting process parameters for each semiconductor layer of a semiconductor device corresponding to a run path formed by different lithographic apparatus which sequentially process target semiconductor layers from a first target layer to a latest target layer; measuring overlay errors between an actual and a theoretical exposed patterns of the first semiconductor layer; selecting a group of process parameters corresponding to the run path from the first target layer to the latest target layer aligned by the current semiconductor layer; after exposing the current semiconductor layer using the selected process parameters, measuring overlay errors between the current semiconductor layer and its target layer; and correcting the selected process parameters according to the overlay errors between the current semiconductor layer and its target layer, and the overlay errors between the actual and theoretical exposed patterns of the first semiconductor layer.