Femtosecond laser has gradually become a reliable tool for processing high-quality film cooling holes (FCHs) of turbine blades in recent years. However, in the case of turbine blades with a variety of aperture drilling requirements, the influence of aperture on drilling quality and its internal causes are ignored. In this paper, the “size effect” of different aperture holes prepared by femtosecond laser helical drilling method was analyzed and compared in terms of geometric features, machining efficiency, hole wall ablation and drilling evolution process, and the formation mechanism of the “size effect” were revealed from the aspects of removal efficiency, laser spot overlap rate, energy shielding effect and residues discharge capacity. The results show that with the increase of laser scanning diameter D, the taper of the hole increases, the drilling efficiency increases first and then decreases, and the surface of hole wall is transformed from microvoids, microcracks and adhesive oxide residues into a regular nanostripes. The increase of D makes the radial spot overlap rate Pr decrease significantly, and Pr seriously affects the removal efficiency and thermal effect on the hole wall, which should be adjusted according to different apertures. Thermal accumulation and laser energy utilization rate attenuation caused by the energy shielding effect are the most important factors that deteriorate the processing quality and reduce the processing efficiency during femtosecond helical drilling. Therefore, for smaller aperture drilling, the strategy of process adjustment is to increase residues discharge capacity.