Oral inhalation of aerosolized drugs can be directly performed on the affected body organs including lesions of the throat, trachea as well as lungs. As compared to the other conventional therapies such as intravenous drip, intramuscular injection and external topical administration, this novel technique can greatly reduce the dosage and side effects of drugs. However, the traditional atomization devices always exhibit many drawbacks, such as wide spreading distribution of atomization particle size, the instability of transient atomization quantity and difficulties in precise energy control, which seriously restrict more extensive application of atomization inhalation therapy. The formation and separation process of droplets is a microphenomenon of atomization. Research on the droplet formation and separation process will help us to better understand the atomization mechanism. In present work, the Conservative Level Set Method (CLSM) is the first time to be applied on the simulation of the formation and separation of droplets in a medical piezoelectric atomization device induced by intra-hole fluctuation. The intra-hole fluctuation mechanism is analyzed in details, and also the expression of the volume change of the micro cone hole is evaluated. The control equation and simulation model of droplet formation and separation process has been well established by meshing the simulation model, and thereby the process of droplet formation and separation is simulated. The corresponding results demonstrate that the breaking time of droplets decreases with the increase of inlet velocity and liquid temperature, and increases with the increase of liquid concentration. Meanwhile, the volume of droplet decreases with the increase of inlet velocity and liquid concentration, but increases with the increase of liquid temperature. The velocity of droplet is enhanced with the inlet velocity and liquid temperature rising, and reduced with the increase of liquid concentration. When the large side diameter of micro-cone hole is set as 79 μm, the breaking time of the droplet reaches a minimum value of 38.7 μs, whereas the volume and the velocity of droplet reaches a maximum value of 79.8 pL and 4.46m/s, respectively. This study reveals the atomization mechanism of the medical piezoelectric atomization device induced by intra-hole fluctuation from a micro perspective . It provides theoretical guidance for the design of medical piezoelectric atomization devices and contributes to the promotion of inhalation therapy in practical use.