A series of novel self-healing pH-sensitive biodegradable hydrogels based on cytosine (C) and guanosine (G) modified hyaluronic acid (HA) is prepared via hydrogen bonding under physiological conditions, with 1,6-hexamethylenediamine (HMDA) as a bridging unit between nucleobase and HA. The lowest gel concentration, gelling time, pH-sensitivity, self-healing behavior, Theological properties, morphology, swelling ratio, degradation kinetics, and drug delivery behavior of HA-HMDA-C, HA-HMDA-G, and HA-HMDA-C/G hydrogels are investigated. The results demonstrate that moderate gelation time and rheology properties are observed at a concentration of 10% (w/v) hyaluronic acid derivative hydrogels. Most of the properties of HA-HMDA-C/G hydrogels are superior to the properties found in HA-HMDA-C and HA-HMDA-G at the same concentration of hydrogel. Overall, the series of pH-responsive self-healing hydrogels exhibits suitable gelling time, good rheology properties, high swelling ratio, biodegradability, effective drug loading capacity, and sustained drug release ability under physiological conditions, signifying that these hydrogels could be attractive candidates for short- and medium-term injectable drug delivery systems, tissue engineering, cell scaffold materials, and regenerative medicine. (C) 2016 Elsevier Ltd. All rights reserved.