Objective To study the role of P2X4 receptor (P2X4R) in a cell model of Parkinson’s disease (PD). Methods Treat human neuroblastoma cells SH-SY5Y with 6-hydroxydopamine (6-OHDA) to establish a Parkinson’s disease cell model and detect the expression of P2X4R. P2X4R was silenced in SH-SY5Y cells, cell viability was detected by cell counting kit 8 (CCK-8), cell apoptosis was detected by flow cytometry, and the expression of apoptosis factors and pannexin 1 (PANX1) was detected by Western blotting. Western blotting was used to detect the expression of Toll-like receptor 2 (TLR2) protein when P2X4R was silenced, P2X4R was inhibited and PANX1 was overexpressed. TLR2 was overexpressed in PD model cells, and cell viability, apoptosis, and apoptotic factor expression were examined. Results P2X4R protein and mRNA expression levels in PD model cells treated with 100 and 150 μmol/L 6-OHDA were higher than those in control group (all P＜0.05). After P2X4R silence, the apoptosis of PD model cells was significantly decreased and cell survival rate was significantly increased; and the protein expression of cysteine aspartic acid specific protease (caspase) 3, cleaved caspase 3 and PANX1 was significantly decreased (all P＜0.05). The expression of TLR2 protein in PD model cells was decreased after silencing P2X4R and inhibiting P2X4R (both P＜0.05). The expression of TLR2 protein was significantly decreased after PANX1 overexpression (P＜0.05). After TLR2 overexpression, the protein expression of caspase 3 and cleaved caspase 3 was significantly decreased (both P＜0.05), and the cell survival rate was increased. Conclusion P2X4R may reduce apoptosis of PD model cells by regulating PANX1 and TLR2 expression.