BACKGROUND: Medial temporal lobe epilepsy (MTLE) is the most frequent type of epilepsy. In recent years, the important roles of lncRNAs in regulating human diseases progression had been implicated, including in epilepsy. However, comprehensive analysis of differentially expressed lncRNAs in Medial Temporal Lobe Epilepsy was still lacking. OBJECTIVES: The aim of this study was to explore relevant lncRNAs in MTLE. METHODS: In present study, we analyzed a public dataset GSE25453 to identify differentially expressed lncRNAs and mRNAs in the MTLE. RESULTS: A total of 16 lncRNAs (C6orf176, NCRNA00259, PRO1768, TTTY11, LOC149620, GDEP, LOC400891, HLA-DRB6, TTTY21, TTTY3, NBR2, TTTY1, FAM183B, C15orf51, FAM74A3, and MALAT1) were identified. LncRNA co-expression network analysis showed these lncRNAs were mainly enriched in regulating transcription, inflammatory response, DNA binding, Jak Stat Signaling Pathway, and Mapk Signaling Pathway. Meanwhile, lncRNA-mRNA-biological processes networks were also performed to evaluate the potential roles of key lncRNAs in MTLE. CONCLUSIONS: This study will be useful to explore the potential candidate biomarkers for diagnosis, prognosis, and drug targets of MTLE.