To investigate the color reactions between naturally cross-linking agent genipin and silk sericin (SS), a series of genipin/SS film with adjustable color were firstly fabricated and analyzed by FTIR, UV/Vis and colorimetric methods. Then under the various genipin/SS contents, double cross-linked genipin/SS/Poly(N-isopropyl-acrylamide/N,N'-Methylene-bis-acrylamide) (HMGX) hydrogels were prepared, and the SEM, DSC, gravimetric and MTT method were performed to investigate pore structure, swelling behavior, temperature-sensitivities and cell adhesion behavior of HMGX hydrogels. The results show that SS cross-linked by genipin presents various colors during reaction. With increasing genipin/SS from 0 to 20 wt% or reacted time from 0 to 250 mm, the color of genipin/SS mixture solution changes from transparent yellow to green, then to skyblue and finally became dark blue. After SS was cross-linked genipin, the maximum absorption peak turns to 570-600 nm from 282 nm, the reacted gardenia blue shows thermo/pH stable and water soluble. The absorption values of genipin/SS solutions increase, especially as genipin/SS ratio is 20 wt%, sharply increase can be found. The reaction time or rate between sericin and genipin is dependent on genipin/SS feed ratios. And with increasing mass percentage of genipin/(NIPAm + SS) from 0 to 10 wt%, due to high hydrophilicity of cross-linked product between genipin and SS, the pore sizes of HMGX hydrogels increase 1-3.75 times, the maximum swelling ratios (MSR) values increase to 2243% from 1057%. The volume phase transition temperature (VPTT) values of HMGX hydrogels keep still at 32-36 degrees C, but the endothermic peak becomes broader. After adsorption of L929 cells for 4 h and 1 d, the hydrogel with 3 wt% of genipin/(NIPAm + SS) presents the highest adhesion percentage. (C) 2015 Elsevier B.V. All rights reserved.