The mechanism of the occurrence and development of neonatal brain injury remains largely unknown, but the inflammatory damage has been recognized to play an important role. As an important receptor for the innate immune response, the Toll-like receptor-related signaling pathway is closely related to the activation of inflammation. Toll-like receptor family members TLR2, TLR3 and TLR4 could promote the expression of inflammatory cytokines through various mechanisms, thereby affecting the progression and prognosis of neonatal brain injury. The authors now review the research progress of TLR 2, TLR 3 and TLR 4 in neonatal brain injury, in order to provide help for the mechanistic understanding of the disease, and also provide some ideas and reference for the drug development of targeted Toll-like receptors that can be used in the treatment of neonatal brain injury.