The present disclosure provides a laser lift-off method for separating substrate and semiconductor-epitaxial structure, which includes: providing at least one semiconductor device, wherein the semiconductor device includes a substrate and at least one semiconductor-epitaxial structure disposed in a stack-up manner; irradiating a laser onto an edge area of the semiconductor device to separate portions of the substrate and the semiconductor-epitaxial structure in the edge area; and pressing against the edge area of the semiconductor device vis a pressing device, then irradiating the laser onto an inner area of the semiconductor device to separate portions of the substrate and the semiconductor-epitaxial structure in the inner area wherein gas is generated during separating the portions of the substrate and the semiconductor-epitaxial structure in the inner area and evacuated from the edge area, to prevent damage of the semiconductor-epitaxial structure during the separating process.