The major depressive disorder (MDD) is a relatively common mental disorder from which that hundreds of million people have suffered, leading to displeasing life quality, which is characterized by health damage and even suicidal thoughts. The complicated development and functioning of MDD is still under exploration. Long noncoding RNA (IncRNAs) are highly expressed in the brain, could affect neural stem cell maintenance, neurogenesis and gliogenesis, brain patterning, synaptic and stress responses, and neural plasticity. The dysregulation of certain IncRNAs induces in neurodevelopmental, neurodegenerative and neuroimmunological disorders, primary brain tumors, and psychiatric diseases. Although advances have been made, no fully satisfactory treatments for major depression are available, further investigation is requested. And recently data showed that the expression level of the majority of IncRNAs demonstrated a clear tendency of upregulation, and the certain dysregulated miRNAs and lncRNAs in the MDD have been proved to have a co-synergism mechanism, that is why we speculate IncRNA might get the capability to regulate MDD. Few identified IncRNAs have been deeply studied in detailed experiments up until now, little predictions of their function have been raised, and further researches is calling for discover their signal pathway and related regulatory networks. (C) 2016 Elsevier Inc. All rights reserved.