Long non-coding RNAs (lncRNAs) are a complex and diverse group of transcripts, typically longer than 200 nucleotides, which do not encode proteins but play crucial roles in regulating gene expression. They exert their influence through various mechanisms, such as interacting with DNA, mRNA, and proteins, which allows them to modulate a wide array of biological processes. Recent studies have underscored the importance of lncRNAs in the development of the nervous system and the pathogenesis of neurological diseases, particularly in the context of hypoxic-ischemic brain injury. Hypoxic-ischemic brain injury, caused by reduced blood flow and oxygen supply to the brain, is a leading cause of long-term neurological deficits. This review delves into the emerging role of lncRNAs in hypoxic-ischemic brain injury, exploring how these non-coding RNAs influence critical molecular and cellular pathways involved in the brain's response to hypoxia-ischemia. Notable advancements, such as the identification of lncRNAs, like BC088414 and FosDT, highlight their dual roles as mediators of injury and potential therapeutic targets. Additionally, we discuss the feasibility of lncRNAs as biomarkers for early diagnosis and prognosis of hypoxic-ischemic brain injury. Despite these advancements, challenges remain in translating lncRNA research into clinical applications. Issues, such as delivery mechanisms, off-target effects, and the ethical considerations surrounding gene modulation, must be addressed. By synthesizing current research, this review aims to provide a comprehensive understanding of the multifaceted roles of lncRNAs in hypoxic-ischemic brain injury, paving the way for future research and novel therapeutic strategies targeting these non-coding RNAs in neurological disorders.