Cell tensegrity model has been widely accepted as a qualitative and recently quantitative method to describe the cellular mechanics. It is based on the fact the cell body is an inhomogeneous cytoskeleton based structure bounded by a soft membrane. Cell establishes force balance under certain structural arrangement through its focal adhesions and intercellular adhesions, under which the prestress is the main factor in determining the cell mechanical property as a whole. Here we demonstrate that intercellular adhesion is one of the main mechanisms employed by epithelial cells to achieve balance. We use keratinocytes as the model system to study this cellular behavior. It is found that loss of intercellular adhesion by desmosome disruption will cause the structural rearrangement of the cytoskeleton and subsequently lower the prestress in the whole cytoskeletal structure, thus change the mechanical property, in this case decrease of stiffness. The loss of intercellular adhesion causes was achieved by three different mechanisms either biochemical or biomechancal. Biochemically, antibody binding and calcium depletion would cause the disruption or non-formation of desmosome, which leads to loss of welding point of intermediate filaments. Biomechanically, intermediate filaments bundles were cut off by Atomic Force Microscopy (AFM) based nanodissection. All these mechanisms verified that the cell stiffness drop afterintercellular adhesion loss. Further, simulation results by a 6strut tensegrity structure with or without intermediate filaments confirmed the experimental findings, where structures with intermediate filaments are stiffer overall. This study would significantly enhance our understanding of the cell cytoskeleton mechanics.