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Under the dual pressure of energy consumption and environmental pollution, mankind hopes to develop clean and renewable alternative energy, and the rapid development of fuel cells meets people's demand for energy-efficient power systems. The emergence of portable micro energy systems represented by microfluidic fuel cells, such as paper-based microfluidic fuel cells, has greatly enriched the means of medical detection to better cope with the threat of disease transmission. In this work, the numerical simulation method is innovatively introduced to study the paper-based microfluidic fuel cells. Both transient and steady-state modes are employed to demonstrate the whole operation process of the paper-based microfluidic fuel cell. In addition, the different structural parameters, including electrode spacing, the distance between electrode and inlet, channel thickness, and electrode length, are also investigated their influence mechanisms on cell performance. Results show that the increase of most structural parameters decreases cell output power in different degrees. Even on the premise that increasing channel thickness has a positive impact on the output power, the fuel utilization still shows a downward trend. These conclusions provide theoretical support and reference for future optimization work and accelerate the development of microfluidic fuel cells. • Numerical simulation is employed to study paper-based microfluidic fuel cell. • The effects of structure parameters on cell performance are discussed. • Through fuel concentration distribution to reveal cell performance mechanism. • Fuel utilization is used to evaluate energy efficiency. [ABSTRACT FROM AUTHOR]