Abstract: OBJECTIVE To study the preparation technology of sustained release biodegradable triptorelin microsphere prepared by hot-melt extrusion and its quality. METHODS First, conduct the single factor experiments to screening correlation parameters such as the kind of frame materials PLGA, PLGA and triptorelin weight ratio, hot melt extrusion temperature and time, grinding temperature and other parameters. On this basis, conduct orthogonal test about hot melt extrusion time, hot melt extrusion temperature, cooling temperature, to screen more accurate process conditions. The quality and stability of the newly designed microsphere were investigated by the influential factor test, accelerated test and long-term test. RESULTS The microspheres prepared by hot-melt extrusion had good morphology. And in the stability test, the content of related substances was in the required range and the accumulative dissolution was good. CONCLUSION The quality of sustained release biodegradable triptorelin microsphere prepared by hot-melt extrusion is stable and suitable for further development. Through these studies, provided a theoretical and practical basis for the safe and effective quality control on microspheres preparation.