Parkinson’s disease (PD) is commonly characterized by motor movement deterioration and cognitive impairment. A dopamine-derived endogenous neurotoxin, namely salsolinol was found contributing to pathogenesis of the disease. However, the precise molecular mechanisms of the neurotoxin remain unexplored. Hence, this study aims to evaluate the effect of salsolinol on SH-SY5Y neuronal cells, focusing on oxidative stress-associated apoptotic cell death. Salsolinol was added to SH-SY5Y cells for determination of cell proliferation and viability using cell growth curve and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays respectively. Cell cycle analysis was performed to measure cell cycle phase distribution while presence of apoptotic cell death was confirmed with Hoechst stain. Additionally, 2’,7’-dichlorofluorescein diacetate assay was carried out to investigate generation of reactive oxygen species (ROS) and enzyme-linked immunosorbent assay was performed to determine the expression of superoxide dismutase (SOD), NF-E2 related factor 2 (Nrf2) and kelch-like ECH-associated protein 1 (Keap1) proteins. Results reveal that SH-SY5Y cells, when treated with salsolinol (0-100 μM) for 24, 48 and 72 hours elicited neurotoxicity. The reduction and inhibition of cell growth and induction of apoptosis were coincided with enhanced ROS production and increased SOD, Nrf2 and Keap1 proteins expression. Thus, it is suggested that salsolinol can induce oxidative stress-associated apoptotic cell death via SOD, Nrf2 and Keap1 activation