Among the parameters that affect the ventilation capacity of an underground mine, the cross-sectional shape of the roadway plays a significant role. When the required airflow is constant, the roadways with different shapes but the same area evidently overcome the different wind resistance. In order to investigate the influence of roadway cross-sectional shape on airflow resistance, this study carried out experimental and Simulation Research on the influence of different cross-section shape and size changes on ventilation resistance. And the Relative Shape Factor (RSF) is established to quantitatively evaluate the influence of cross-section shape on ventilation resistance. Firstly, focusing on the four common types of cross-sectional in the roadway, including circular, rectangular, trapezoidal, and arched, the experimental platform of airflow resistance of the pipe is built, and the effect of the changes of cross-sectional shape on the ventilation resistance is studied. Furthermore, the law of airflow resistance with different scale changes under the same section shape is studied by numerical simulation. Subsequently, the scale-independent coefficient RSF is established through theoretical derivation to characterize the degree to which the section shape deviates from the circle. The further it deviates from the circular shape, the larger the RSF, indicating a greater impact of the cross-section shape on airflow resistance. Comparing the theoretical with the simulation results, the RSF errors of the rectangular, trapezoidal, and arched shapes are 7.3%, 4.01%, and 2.05%, respectively, indicating that the RSF can accurately describe the influence of the cross-section on ventilation resistance. Finally, the range of RSF for common roadway dimensions is summarized, the trapezoidal is 1.131 to 1.187, the arch-shaped is 1.0 to 1.160, and the rectangular is 1.128 to 1.152. The proposed RSF in this paper is intuitive and effective, which provides a reference for the engineering application and a new insight for the selection of the minimum ventilation resistance cross-section of roadway.