IgG4-related disease (IgG4-RD) is distinguished by the infiltration of IgG4-positive plasma cells in a variety of tissues and organs. Even so, central nervous system lesions associated with IgG4-RD are scarce. We present a case of IgG4-related brain parenchymal lesions that mimics multiple sclerosis in a young girl. The patient was followed by our neurology and rheumatology teams. Clinical information was recorded, and the brain was screened using magnetic resonance imaging (MRI). During follow-up, we examined serum IgE, IgG and IgG4 and lymph node biopsy. Here, we presented details of a 14-year-old Chinese girl suffering from diplopia, left eyelid ptosis, right facial numbness, and right lower limb weakness admitted to our institute. Brain MRI revealed multiple sclerosis-like lesions in the brain parenchyma and spinal cord. During the follow-up, she developed lymphadenopathy. Elevation of serum, IgG, IgG4 and IgE and lymph node biopsy favors a diagnosis of IgG4-RD. The patient had a good response to glucocorticoids and mycophenolate mofetil. The literature review summarized eight previously reported IgG4-RD involving brain parenchyma. Our case expands the known age spectrum of IgG4-RD. The intracranial IgG4-RD is rare and could mimic multiple sclerosis. Careful examination and dynamic review of disease history are crucial in the differential diagnosis.