Alterations of cell volume induced by either aniso-osmotic environments or under the influence of hormones, concentrative amino acid uptake and oxidative stress were recognized as an independent signal contributing to the regulation of metabolism and gene expression. The regulation of cell function by hydration changes requires structures, which register fluctuations of cell hydration (osmosensing) and thereby activate intracellular signalling pathways towards effector sites (osmosignalling). Meanwhile, it is well established that osmosensing and signalling integrate into the overall context of hormone- and nutrient-induced signal transduction. Recent evidence suggests integrins to play a major role in osmosensing and signalling due to hepatocyte swelling. This review focuses on the role of integrins in sensing of hepatocyte swelling as triggered by hypo-osmolarity, glutamine and insulin and the relevance of integrin-dependent osmosignalling for inhibition of autophagic proteolysis, stimulation of canalicular bile acid excretion and regulatory volume decrease.