The dysfunction of stress granules (SGs) plays a crucial role in the pathogenesis of various neurological disorders, with T cell intracellular antigen 1 (TIA1) being a key component of SGs. However, the role and mechanism of TIA1-mediated SGs in experimental autoimmune encephalomyelitis (EAE) remain unclear. In this study, upregulation of TIA1, its translocation from the nucleus to the cytoplasm, and co-localization with G3BP1 (a marker of SGs) are observed in the spinal cord neurons of EAE mice. Deletion of TIA1 in the CNS alleviates neuroinflammation, suppresses demyelination and axonal damage, and reduces neuronal loss in EAE mice. Furthermore, alleviation of autophagy dysfunction and reduction of chronic persistent SGs are observed in Tia1Nestin-CKO EAE mice. Mechanistically, IL-31RA levels are decreased in Tia1Nestin-CKO EAE mice, which inhibit the downstream PI3K/AKT signaling pathway associated with IL-31RA, thereby enhancing autophagy and suppressing the NF-kappa B signaling pathway, further alleviating EAE symptoms. Knockdown of TIA1 in primary neurons and N2a cells treated with sodium arsenite also reduces the formation of SGs. These findings reveal an unrecognized role of TIA1-mediated SGs in promoting neuroinflammation and demyelination, offering novel therapeutic targets for MS.