Rationale:Multiple sclerosis (MS) is a central nervous system disease mainly mediated by immunity, which is one of the most common causes of neurological dysfunction in young people worldwide. In the acute phase, high-dose steroid therapy is effective. There are few reports about cerebral venous thrombosis (CVT) after high-dose steroid therapy.Patient concerns:We present a case of a 19-year-old female diagnosed with MS who developed a headache after high-dose steroid therapy was diagnosed with CVT. Headache symptoms improved after anticoagulant treatment.Diagnoses:MS comorbid CVT.Interventions:Anticoagulant therapy was added and hormone therapy was reduced.Outcomes:Clinical symptoms such as headache, limb numbness, and involuntary tremors in the right hand were improved, and the muscle strength of the right limb recovered to grade 4. The patient did not suffer from headaches after discharge and no abnormality in the computed tomography (CT) scan of the cephalic vein at the 5-months follow-up.Lessons:High-dose steroid therapy may be a risk factor for CVT in patients with MS. MS patients who develop headaches during high-dose steroid therapy should undergo further cranial CTV to rule out CVT.