Abstract: Objective To detect the differential gene expression of sclerosis hippocampus in patients with refractory mesial temporal lobe epilepsy(MTLE) and normal hippocampus by gene chip technique, and explore the pathogenesis of temporal lobe epilepsy from the genetic aspect. Methods From April 2015 to June 2017, three sclerosis hippocampus obtained from patients with MTLE who underwent refractory temporal lobe epilepsy surgery and three normal hippocampus obtained from autopsy were collected in our study. Total RNA was extracted from the samples, and cDNA was synthesized by reverse transcription. After fluorescent labeling, the chip was used to detect differentially expressed genes. The differentially expressed genes were verified by qRT-PCR assay. GO function and Pathway analysis were further performed based on the differential expression of mRNAs using bioinformatic software. Results Compared with normal hippocampus, 399 mRNAs differentially expressed in sclerosis hippocampus, consisting of 236 upregulated and 163 downregulated mRNAs(fold-change>2.0 or<-2.0, P<0.05). The highest and lowest differential expressing genes were CPLX3 and DCDC5, respectively. The functions and pathways involved in differential genes included inflammatory response, signal receptor activity, neuropeptide receptor activity and signaling pathway, neuroactive ligand-receptor interaction pathway, and calcium signaling pathway. Conclusion Compared with normal hippocampus, the genes significantly and differentially express in sclerosis hippocampus in patients with MLTE. Go function and pathway analyses of differential expression genes can reveal the pathogenesis of MTLE.