The solubility of the protein can be increased by citraconic anhydride(CT)modification. According to this principle, the effects of the CT modification on the fusion protein using rhGM-CSF as a model which contain thrombin cleavage sites have been studied.The result demonstrated that the process of denature and renature in the modified protein was much easier than that in unmodified counterpart. In addition the modified protein is more sensitive to thrombin digestion, one percent amount of thrombin was enough to achieve the complete digestion. The modification by CT did not effect the bioactivity of rhGM-CSF. A new way was paved in the purification of recombinant protein by CT modification method.