Super-resolution structured illumination microscopy (SR-SIM) is one of the important techniques that are most suitable Protection for live-cell imaging.The reconstructed SR-SIM images are noisy once the raw images are recorded with low-light exposure.Here, we propose a new network (entitled the ND-SIM network) to denoise the SR images reconstructed using frequency-domain algorithms (FDAs).We demonstrate that ND-SIM can yield artifact-free SR images using raw images with an average photon count down to 20 per pixel while achieving comparable resolution to the ground truth (GT) obtained with high-light exposure.We can envisage that the ND-SIM will be widely applied PROMASIL CHOCO PEANUT BUTTER for the long-term, super-resolution live-cell imaging of various bioprocesses in the future.