Silicone modified polyurethane (PUSX) has attracted interest as a useful material by various properties, which are combined with silicone and polyurethane. In this paper, we tried to optimize the electrospinning process of silicone modified polyurethane (PUSX) nanofibers on a lab scale device and a multinozzle pilot scale set-up to investigate the potential and limitations of preparing PUSX nanofibrous sheets using different equipment. The morphology and diameter of the obtained fibers were studied via scanning electron microscopy (SEM). Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was also carried out to analyze the chemical structure of PUSX nanofibers. As a result, we successfully figured out the optimal parameters of PUSX electrospinning process and demonstrated the great potential of the process for mass production of PUSX nanofibrous sheets from solutions.