〔Abstract〕 Objective To investigate the role of E2 F transcription factor 1(E2 F1) in hemin-induced primary cortical neuron injuries and the possible mechanisms in rats. Methods Rat primary cortical neurons were cultured, identified and treated with different concentrations of heminin vitro. LDH and MTT assays were performed to detect cell damage when neurons were treated for 12 h. The location and the expression of E2 F1 in neurons were detected by immunofluorescence double staining and Western blot respectively. Rats were divided into vehicle group(DMSO), injury group(Hemin), negative control group(Hemin+Control siRNA) and treatment group(Hemin+E2 F1 siRNA). TUNEL staining and caspase activity were performed in four groups. Results The positive rate of NeuN staining was 95% on the 7 d. With the treatment of hemin(50, 100, 200 μmol/L), the LDH release of neurons increased, cell viability decreased and E2 F1 expression was up-regulated(F=22.9,P<0.05). Compared with the negative control group, LDH release decreased [(73.6±5.2)%vs(42±4.1)%,F=343.4,P<0.05] and the cell viability increased [(28.7±3.4)%vs(61±2.9)%,F=127.7,P<0.05] in the E2 F1 siRNA-treated group. The TUNEL results showed that hemin treatments increased neuronal apoptosis, and E2 F1 siRNA treatments reduced the apoptosis(F=67.2,P<0.05). The caspase activity assay showed that the activities of caspase-3, caspase-8 and caspase-9 in the hemin group increased(t=15.7,t=9.7,t=7.8,P<0.05), but E2 F1 siRNA treatment decreased the activities of caspase-3, caspase-8 and caspase-9(t=8.6,t=7.3,t=5.7,P<0.05). Conclusion E2 F1 siRNA may play a neuroprotective role by inhibiting hemin-induced neuronal apoptosis.