Local anaesthetics are known to produce neurotoxicity at normal doses. Present investigation check the neuroprotective effect of P2X4 receptor antagonist in local anaesthetic induced neurotoxicity. In this study SH-SY5Y neuronal cell was treated with local anaesthetic (bupivacaine) and P2X4 receptor antagonist (Sumarin) at different concentrations. Neuroprotective effect of sumarin was evaluated by estimating cell viability, apoptosis, Reactive Oxygen Species (ROS) accumulation, Caspase 3 and 9 activity and morphological changes. Result of study suggested that treatment with sumarin significantly increases (p<0.01) the cell viability and reverse the effect of bupivacaine. It was observed that treatment with sumarin (100 μmol/l) effectively attenuates the apoptosis, ROS accumulation Caspase 3 and 9 activity and morphological changes induced by bupivacaine (1 mmol/l). Thus present study concludes that neuroprotective effect of P2X4 receptor antagonist in bupivacaine induced neurotoxicity of cell by decreasing the ROS and Caspase activity and thereby decreases the apoptosis of neuronal cell.