The overexpression of the multidrug resistance gene (MDR-1) and its translational product p-glycoprotein (P-gp) may play an important role in pharmacoresistant epilepsy. We established the rat astrocyte model overexpressing P-gp induced by coriaria lactone and successfully nucleofected it with the siRNA-hairpin expression vector pSIREN-shuttle designed to target MDR-1B mRNA. The mRNA expression of MDR-1B gene was mostly knock down by 67.70% (p<0.01). The expression of P-gp in experimental group was significantly lower than that in negative control (p<0.05), and the rhodamine efflux ratio of experimental group (23.08%) was remarkably lower than that of negative control (78.35%, p<0.01). We first employed RNA interfering to the drug resistance reversal of refractory epilepsy and this may provide a new way for refractory epilepsy remedy.