Microfluidic systems for biochemical reactions require efficient microfluidic actuation. However, current microfluidic devices are facing challenges in terms of self-powering and precise transport of microfluidics. This study demonstrates a novel approach to fabricating a self-powered and precise microfluidic manipulation system based on triboelectric nanogenerator (TENG) and electrowetting-on-dielectric (EWOD) technologies. The TENG provides high pulsed voltage and electrical wetting capabilities, enabling the manipulation system to drive microfluidic transport through electric field forces. The self-powered microfluidic device is systematically investigated by the effect of various parameters, including TENG power, TENG structures, EWOD/microfluidic device structures and surface hydrophobic properties. By optimizing the parameters, optimal performances are achieved in microfluidic motion, particularly in terms of precise two-dimensional movement. The movable volume range spans from 20   nl to 1.4   ml, representing one of the most notable achievements of TENG in the field so far. Additionally, the self-powered microfluidic system successfully synthesized multiple morphological ZnO nanoparticles, a rarely reported accomplishment. Finally, the novel self-powered system demonstrates the capability to detect chloride in disinfected water and COVID-19 antigen detection. This work proposes a novel TENG-EWOD microfluidic control technology that shows promise in various applications, including chemical processes, biological health testing and microdevice fabrication.