OBJECTIVE: To explore the effect of pretreatment of neuroblastoma cells with hot water extract of Korean ginseng on MNNG-induced parthanatos and its mechanism. METHODS: Neuroblastoma SH-SY5Y cells were pretreated with 1 mg/L hot water extract of Korean ginseng before induction with 250 μmol/L MNNG for 1 h or 4 h. CCK-8 and cell flow cytometry were used to detect cell survival rate. Western blotting was used to detect the changes in poly(ADP-ribose) (PAR) expression in the treated cells. Immunofluorescence assay was used to detect nuclear distribution of apoptosis-inducing factor (AIF), and flow cytometry was used to detect the level of reactive oxygen species (ROS) in the cells. RESULTS: Compared with the blank control cells, MNNG-treated SH-SY5Y cells showed significantly decreased survival rate as the concentration of MNNG and the stimulation time increased ( < 0.05). Stimulation with MNNG also resulted in significantly increased expression of PAR protein in the cells ( < 0.05). Pretreatment of the cells with hot water extract of Korean ginseng obviously inhibited MNNG-induced cell death and significantly reduced AIF expression and nucleation in the cells ( < 0.05). MNNG stimulation significantly increased ROS level in the cells, which was decreased significantly by pretreatment of the cells with the extract ( < 0.05). CONCLUSIONS Pretreatment with hot water extract of Korean ginseng reduces MNNG-induced parthanatos and ROS production in SH-SY5Y cells.