Various biodegradable hydrogels have been employed as injectable scaffolds for tissue engineering and drug delivery. We report a double-crosslinking strategy of biocompatible and biodegradable hydrogels derived from aminated and oxidized hyaluronic acid (HA) with genipin (GP), a compound naturally derived from the gardenia fruit. Fast gelation is attributed to the Schiff-base reaction between amino and aldehyde groups of polysaccharide derivatives, and the subsequent crosslinking with GP results in ideal biodegradability and mechanical properties. The gelation time, morphology, equilibrium swelling, compressive modulus and degradation of double-crosslinked hydrogels were examined. The double crosslinked hydrogels were examined in vivo via subcutaneous injection into a mouse model. Histological results indicated favourable biocompatility, as revealed by an absence of neutrophils and macrophages. These studies demonstrate that double-crosslinked HA hydrogels are potentially useful as injectable, biodegradable hydrogels in tissue-engineering applications. Copyright © 2011 John Wiley & Sons, Ltd.