Objective To explore expression of HMGB1 and TLR4 in epileptogenic focus brain tissue of temporal lobe intractable epilepsy patients, and analyze its significance in epileptic seizures. Methods 85 tempo-ral lobe intractable epilepsy patients were included in the research. Patients underwent resection of epileptogenic focus in Neurosurgery Department of The Fifth Affiliated Hospital of Zhengzhou University during January 2011 to January 2012. Epileptogenic focus brain tissue during operation were studied. 20 patients underwent intracranial decompression were selected as control group. Normal brain tissue during operation were studied. Immunohisto-chemical method was applied to detect HMGB1 and TLR4 expression level in epileptogenic focus brain tissue of ex-perimental group patients and normal brain tissue of control group patients. Correlation of HMGB1 and TLR4 expres-sion level and epileptic seizures was analyzed. Results Positive expression rate of HMGB1 (χ2= 74.375, P =0.000) and TLR4(χ2= 57.495, P = 0.000) in epileptogenic focus brain tissue of experimental group patients are both higher than that in normal brain tissue of control group patients. Expression of HMGB1 and TLR4 in epilepto-genic focus brain tissue is correlated with course of epilepsy (χ2= 25.798, P = 0.000), (χ2= 10.548, P = 0.001) preoperative epileptic seizure duration(χ2=8.403, P=0.004),(χ2=10.564, P= 0.001) and preoperative epilep-tic seizure frequency (χ2=4.912, P=0.027), (χ2=5.567, P=0.018). Conclusions HMGB1-TLR4 passageway may become new direction to study pathogenesis, diagnosis, and treatment of intractable epilepsy.