Abstract: Hyaluronan (HA) has wonderful biocompatibility and biodegradability，but needs cross- linking modification to improve its mechanical properties for its use as a biomaterial. This review concentrates on the recent advances of cross-linking reagent for producing HA derivatives，and introduces the application and development of common cross-linking reagent and new type cross-linking reagent，so as to provide more advice for the development of HA reagent.