Knowledge of the mechanical properties of the brain-skull interface is important for surgery simulation and injury biomechanics. These properties are known only to a limited extent. In this study we conducted in situ indentation of the sheep brain, and proposed to derive the macroscopic mechanical properties of the brain–skull interface from the results of these experiments. To the best of our knowledge, this is the first ever analysis of this kind. When conducting in situ indentation of the brain, the reaction force on the indentor was measured. After the indentation, a cylindrical sample of the brain tissue was extracted and subjected to uniaxial compression test. A model of the brain indentation experiment was built in the Finite Element (FE) solver ABAQUSTM. In the model, the mechanical properties of the brain tissue were assigned as obtained from the uniaxial compression test and the brain-skull interface was modeled as linear springs. The interface stiffness (defined as sum of stiffnesses of the springs divided by the interface area) was varied to obtain good agreement between the calculated and experimentally measured indentor force–displacement relationship. Such agreement was found to occur for the brain-skull interface stiffness of 11.45 (mm [to -1]/ Nmm [to 2].). This allowed identification of the overall mechanical properties of the brain–skull interface.