A method employing in-situ film thickness measurement to perform cutter replacement during large area microstructure cutting comprises the following steps: step 110: preparation work; step 120: initial machining of a workpiece (3); step 130: coating of a transparent film (4), and using a cutting tool (1) to flatten the film by means of lathing or milling; step 140: measuring the thickness of the transparent film (4), and machining the workpiece (3); step 150: performing midway cutter replacement: changing a cutter when the cutting tool (1) is worn, and repeating steps 130 and 140; step 160: completing the machining; and step 170: removing the transparent film (4). The method allows an extra-large area, high quality, and high uniformity microstructure cutting machining.