Fluorescence microscopy typically suffers from aberration induced by system and sample, which could be circumvented by image deconvolution. We proposed a novel, to the best of our knowledge, Richardson–Lucy (RL) model-driven deconvolution framework to improve reconstruction performance and speed. Two kinds of neural networks within this framework were devised, which are partially interpretable compared with previous deep learning methods. We first introduce RL into deep feature space, which has superior generalizability to the convolutional neural networks (CNN). We further accelerate it with an unmatched backprojector, providing a five times faster reconstruction speed than classic RL. Our deconvolution approaches outperform both CNN and traditional methods regarding image quality for blurred images caused by out-of-focus or imaging system aberration.