The aim of this study was to create heparin-like chitosan hydrogels (HLCHs) for blood purification. Herein, we prepared two heparin-like chitosans (HLCSs) with various carboxymethyl and sulfate groups, followed by a cross-linking reaction with glutaraldehyde. The synthetic chitosan derivatives were characterized by X-ray photoelectron spectroscopy, gel permeation chromatography, FTIR and NMR The average sulfonation degrees of two HLCSs were 0.69 and 0.94 per sugar unit, respectively. The swelling ratio of the HLCH could reach up to 4800%, and the HLCHs remained a well-defined shape and stable below 170 degrees C. Moreover, the activated partial thromboplastin time and thrombin time results indicated that both of the HLCSs and their hydrogels exhibited excellent thrombus inhibition property. Furthermore, the contact activation and complement activation results also proved that the hydrogels possessed good blood compatibility and had the potential to be used as blood-contacting materials.