Abstract: Objective To explore the effect of short hairpin RNA （shRNA） mediated purinergic receptor P2X ligand-gated ion channel 7 （P2X7R） silencing on cell proliferation， apoptosis and signal pathway in nasopharyngeal carcinoma. Methods After optimization of the transfection conditions of shRNA， two shRNA vector fragments （shRNA-1， shRNA-2） of P2X7R gene were transfected into HONE1 cells， respectively. The HONE1 cells transfected with nonsense sequence was assigned as empty transfection group and cells without any treatment was used as control group. Quantitative real-time PCR （QPCR） was used to detect the expression of P2X7R at 24， 48， 72 and 96 h after transfection and the infection vector with high inhibition rate was screened for subsequent experiment. The proliferation inhibition rate was detected at 24， 48， 72 and 96 h after transfection by thiazolyl blue （MTT）. The cell apoptosis was detected by flow cytometry at 48 and 96 h after transfection. The mRNA levels of apoptosis related genes were detected by QPCR method. The protein changes of phosphatidylcholine 3-kinase／protein kinase B （PI3K／Akt） pathway and Wnt／β-catenin pathway were detected at 96 h after transfection by Western blotting. Results The level mRNA of P2X7R in transfected group was lower than those in the blank group and the control group （P＜0.05）. The shRNA-1 carrier with high interference efficiency was selected for the functional study. Compared to empty transfection group and control group， there were increased inhibition rate， apoptosis rate and mRNA levels of pro-apoptosis protein bid and Bax but decreased mRNA levels of anti-apoptosis protein Bcl-2 and Mcl-1 in shRNA-1 transfected group with statistical difference （P＜0.05）. Compared with the control group， the protein level of PTEN was elevated and protein level of p-Akt in PI3K／Akt pathway were decreased in shRNA-1 transfection group （P＜0.05）. As for the Wnt／β-catenin pathway， there were decreased expression of p-β-catenin， Cyclin D1 and C-myc in transfection group （P＜0.05）. Conclusion The inhibition of P2X7R gene expression by shRNA can inhibit the proliferation and induce apoptosis， which may be related to the inhibition of PI3K／Akt and Wnt／β-catenin pathway， and it has a certain value for the prevention and treatment of nasopharyngeal carcinoma.