With the development of microfluidic technology, microfluidic chips have played a positive role in applications such as cell culture, microfluidic PCR, and nanopore gene sequencing. However, the presence of bubbles interferes with fluid flow and has a significant impact on experimental results. There are many reasons for the generation of bubbles in microfluidic chips, such as pressure changes inside the chip, air vibration inside the chip, and the open chip guiding air into the chip when driving fluid. This study designed and prepared a microfluidic device based on polydimethylsiloxane. First, air was actively introduced into the microfluidic chip, and bubbles were captured through the microfluidic device to simulate the presence of bubbles inside the chip in biological experiments. To remove bubbles trapped in the microfluidic chip, distilled water, distilled water containing surfactants, and mineral oil were pumped into the microfluidic chip. We compared and discussed the bubble removal efficiency under different driving fluids, driving pressures, and open/closed channel configurations. This study helps to understand the mechanism of bubble formation and removal in microfluidic devices, optimize chip structure design and experimental reagent selection, prevent or eliminate bubbles, and reduce the impact of bubbles on experiments.