Abstract: The present disclosure provides a fusion protein comprising IL-1 receptor antagonist fused to a hybrid Fc. Particularly the present disclosure relates to a fusion protein comprising IL-1 receptor antagonist fused to a human immunoglobulin hybrid Fc fragment. In one embodiment, the hybrid Fc fragment comprises IgD and IgG4. Also provided is a pharmaceutical composition comprising the present fusion protein, which are useful for treating autoimmune disease including rheumatoid arthritis, inflammatory bowel disease (Crohn's disease, ulcerative colitis), psoriasis and diabetes and the like. The present fusion protein with excellent efficacy and reduced side effects is qualified for clinical development as therapeutic antibodies to treat autoimmune disease.