MicroRNAs (miRNA/miR) have an important biological role in the brain where they regulate numerous pathways essential for both development and maintenance. Their altered expression profiles have been observed in a number of neurological impairments, including epilepsy. The aim of our work was to identify miRNAs aberrantly expressed both in mesial temporal lobe epilepsy (mTLE) patients with hippocampal sclerosis (HS) and in rats with pilocarpine-induced epileptogenesis. miRNA expression in samples from mTLE+HS patient was analysed using Next Generation Sequencing technology and validated by miRNA-specific quantitative PCR, miQPCR. We selected 28 miRNAs aberrantly expressed in patients and compared with an animal model (rats with LiCl/pilocarpine induced SE at P60). The miRNAs were isolated from hippocampal tissues from 18 treated rats and 12 age matched controls. Expression of selected miRNAs was quantified using miQPCR. Our quantitative analyses revealed that four of 28 selected miRNAs had significantly aberrant expression in treated rats (miR-19b-3p, miR-142-3p, miR-142-5p, miR-374b-5p) in comparison with controls. miR-142-3p and miR-142-5p were upregulated both in treated rats and in mTLE+HS patients. miR-374b-5p were downregulated in the rat model and upregulated in patients. miR-19b-3p was upregulated only in rat samples. Other miRNAs were not differently expressed in rat model. Our results detected several miRNAs with aberrant expression both in human patients and in the rat model of epilepsy. This comparative analysis significantly increases the confidence that these miRNAs are directly involved in the biology of epilepsy and suggest possible miR-therapeutic targets (miRNA mimics/inhibitors) that could be tested in rat epilepsy model.