Keratin biomaterials support cellular adhesion, proliferation and migration, which have led to their exploitation in a variety of biomedical applications. The mechanism of cell adhesion to keratin biomaterials, however, is poorly understood. Therefore, the goal of this work was to investigate the mechanisms by which human hair keratin-based biomaterials facilitate cellular adhesion. Hepatocytes were used as a model cell type due to the abundance of published data on cell adhesion mechanisms and their relatively copious attachment to keratin substrates. The roles of β 1- and β 2-integrins and the hepatic asialoglycoprotein receptor (ASGPR) in hepatocyte adhesion to keratin substrates were studied using attachment assays with and without function blocking antibodies. Blocking of the hepatic integrin subunits did not decrease hepatocyte attachment to keratin. Furthermore, adhesion to keratin did not result in the formation of focal complexes or focal adhesions, nor did it produce an upregulation of phosphorylated-focal adhesion kinase. However, inhibition of hepatic ASGPR decreased the ability of hepatocytes to attach to keratin substrates, which is indicative of the role of this glycoprotein receptor in hepatocyte binding to keratin biomaterials. © 2011 Elsevier Ltd.