Summary: The LabelHash server and tools are designed for large- scale substructure comparison. The main use is to predict the function of unknown proteins. Given a set of (putative) functional residues, LabelHash finds all occurrences of matching substructures in the entire Protein Data Bank, along with a statistical significance estimate and known functional annotations for each match. The results can be downloaded for further analysis in any molecular viewer. For Chimera there is a plugin to facilitate this process. Availability: The website is free and open to all users with no login requirements at http://labelhash.kavrakilab.org.