Micro-dissection technology possesses revolutionary significance in the research field about Cancer Genomics, through which pure population of targeted cells can be procured from tissue sections for subsequent analysis. In this paper, a novel Micro-dissection technology using ultrasonic vibration was proposed and the piezo-powered micro-dissection tool with its control and drive system were also developed. The micro-dissection tool employs the multilayer piezoelectric actuator for generating the ultrasonic vibration with high frequency and low amplitude. To control the piezo-powered Micro-dissection tool, a driving power for piezoelectric actuator was designed using direct digital synthesizer and direct current amplifying principle, thus the micro-dissection tool could vibrate with the frequency scope from 0.5k to50K and the amplitude scope from 0 to 2μm. Finally, experiments about bio-microdissection on liver tissue slice were carried out with the tool and better micro-dissection result was obtained. The experiments show the feasibility of the micro-dissection method with ultrasonic vibration. The new micro-dissection method can be adopted in the bio-micro-manipulation field and it can also significantly promote the development of Cancer Genomics.