Abstract: OBJECTIVE To explore the effect of the small interfering RNA (siRNA) targeting VP1 gene on cell apoptosis during enterovirus 71 (EV71) infection. METHODS Firstly, siRNA that targeted EV71 VP1 gene was designed and synthesized, then the interfering effect was tested.Secondly, Vero cells were transfected by siRNA and infected by EV71 virus before the cell viability and virus titer were examined to check out whether the infection was inhibited.Furthermore, the cell cycle and phosphatidylserine were examined by flow cytometry to verify the change of apoptosis process.Finally, western blot was carried out to find out the signaling pathways related to the change of apoptosis. RESULTS The siRNA synthesized had an interfering efficiency of 73.3% against VP1 gene.Cells transfected with VP1 siRNA before EV71 infection had a higher viability (38.6% vs.76.1%), lower viral titer (6.1 vs.3.2), lighter cell cycle arrest(31.8±4.0)% vs.(16.9±2.2)% in Sub-G1, and less early apoptosis (43.01% vs.16.00%) as compared to the control group, and upregulated less of AKT/p38 proteins. CONCLUSION Interfering EV71 VP1 gene with siRNA can restrain cells apoptosis through AKT and p38 signaling pathways and lead to inhibition of EV71 infection.