Stiff-Person syndrome (SPS) is a rare and disabling disorder characterized by continuous motor unit activity causing severe rigidity and episodic spasms in axial and limb muscles. It deteriorates the quality of life and causes a serious burden in the patient's life. It is frequently associated with other autoimmune diseases such as diabetes mellitus. Treatment with intravenous immunoglobulin, anti-anxiety drugs, muscle relaxants, anti-convulsants will improve symptoms, but will not cure the disorder. Therapeutic plasma exchange is an alternative treatment for the patients resistant to other treatment options. Here, we report a patient with SPS treated in intensive care unit and underwent therapeutic plasma exchange.