The study presented here aims to identify the microstructural factors which govern the cracking of Tournemire clay-rock caused by humidity changes. A new experimental setup was designed in laboratory to compare the location of desiccation cracks, induced by humidity changes, to the microstructure of a sample (20× 20× 20 mm3) of Tournemire clay-rock. The location of desiccation cracks was measured on a surface of 5.6× 4.2 mm2 by Digital Image Correlation (DIC) and the microstructure was quantitatively estimated by Scanning Electron Microscopy on the same surface. First results show that at millimeter scale the desiccation cracks are divided in two parallel networks: the first network is composed of continuous macrocracks located next to local mineralogical heterogeneities such as the proportion and the mean size of grains, and the second network of discontinuous microcracks at the boundaries between grain/grain, grain/clay matrix or in clay matrix.