Potassium 2-(1-hydroxypentyl)-benzoate (dl-PHPB) has been shown to have potent neuroprotective effects, such as reducing the infarct volume and improving neurobehavioral deficits in the transient focal cerebral ischemic rat model. The present study is to evaluate the neuroprotective effect of dl-PHPB on hydrogen peroxide (H(2)O(2))-induced apoptosis and the possible mechanism in the human neuroblastoma SK-N-SH cells. Our results showed that dl-PHPB significantly attenuated H(2)O(2)-induced cell death, and reduced neuronal apoptosis. Dl-PHPB partially reversed the decrease of B-cell CLL/lymphoma 2 (Bcl-2) protein level induced by H(2)O(2). Furthermore, dl-PHPB inhibited the elevation of pro-apoptotic Bcl-2-associated X protein (Bax) and caspase3, and alleviated the down-regulation of protein kinase C alpha (PKCα). The PKC inhibitor, Calphostin C significantly attenuated the protective effects of dl-PHPB. The findings suggest that dl-PHPB may protect neurons against H(2)O(2)-induced apoptosis by modulating apoptosis-related proteins, and PKC signaling pathway may be involved in the neuroprotection of dl-PHPB.