To review the recent advances of cross-linking reagent for producing hyaluronic acid (HA) derivative so as to provide more advice for the development of HA reagent.Recent original articles related to the species, characteristic, cross-linking methodology and mechanism of the cross-linking reagent to producing HA derivative were summarized and systematically analyzed.The derivatives after special kinds of reagents modification would remain their own good biocompatibility and change their original rheololgical characterization and obtain relative long organism residence time.Development of hyaluronic derivatives may widen their medical application.