25Super-resolution fluorescence microscopy has been instrumental to progress in biology. Yet, the photo-26 induced toxicity, the loss of resolution into scattering samples or the complexity of the experimental setups 27 curtail its general use for functional cell imaging. Here, we describe a new technology for tissue imaging 28 reaching a 114nm/8Hz resolution at 30 µm depth. Random Illumination Microscopy (RIM) consists in 29 shining the sample with uncontrolled speckles and extracting a high-fidelity super-resolved image from the 30 variance of the data using a reconstruction scheme accounting for the spatial correlation of the illuminations. 31 Super-resolution unaffected by optical aberrations, undetectable phototoxicity, fast image acquisition rate and 32 ease of use, altogether, make RIM ideally suited for functional live cell imaging in situ. RIM ability to image 33 molecular and cellular processes in three dimensions and at high resolution is demonstrated in a wide range 34 of biological situations such as the motion of Myosin II minifilaments in Drosophila. 35 36 37 38