Disclosed herein is a method for isolating active regions in a germanium-based MOS device. A surface of a germanium-based substrate is covered by a thin polysilicon layer or a poly-SiGe layer, and an isolation structure of germanium dioxide covered by a silicon dioxide layer or a SiGe oxide layer on top is formed by means of two steps of oxidation in a case of the active regions are protected. Such two steps of oxidation using the polysilicon layer or the poly-SiGe layer as a sacrificial layer is advantageous to improve the isolation quality of a fabricated germanium dioxide and to reduce a beak effect occurred during a local field oxygen oxidation so as to dramatically elevate the performance of the germanium device.