Objective: to study the protective effect of MgSO4 on 6-hydroxydopamine(6-OHDA)induced neurotoxicity in SH-SY5Y cells,and the changes of mRNA and protein expression of magnesium transporters SLC41A1,NIPA1,MagT1 and CNNM2 on 6-OHDA-induced neurotoxicity in SHSY5Y cells.Methods: cell viability under different concentration of MgSO4 and 6-OHDA were measured using cell counting Kit-8.Cultured SH-SY5Y cells were divided into 5 groups: control,50μM 6-OHDA,MgSO4(0.25mM,0.5mM and 1mM,MgSO4 was added 1h before 6-OHDA); the expression of tyrosine hydroxylase(TH)were detect by Western Blot and immunofluorescence.The mRNA and protein expression of SLC41A1,NIPA1,MagT1 and CNNM2 were measured by real-time PCR and Western Blot.The anti-oxidative capacities of SH-SY5Y cell were measured by ABTS [2,2-Azinobis-(3-ethylbenzthiazoline-6-sulphonate)]; the intracellular reactive oxygen species(ROS)level of SH-SY5Y cells was detected using DCFH-DA(2,7-dichlorofluorescin diacetate).Results: SH-SY5Y cells preincubated with 25μM~50μM 6-OHDA 24h could decrease the cell viability(p<0.05,versus control),while 0.125mM~1mM MgSO4 pretreated 1h before 6-OHDA could prevent the cell damage(p<0.05,versus 6-OHDA group).SH-SY5Y treated with 50μM 6-OHDA lead 52.23%loss of TH compared with the control(p<0.05),while MgSO4 can prevent SH-SY5Y from 6-OHDA induced TH loss.The mRNA and protein expression of SLC41A1,NIPA1,MagT1 and CNNM2 in 6-OHDA treated SH-SY5Y were significant decrease.MgSO4 upregulated the expressions of above genes,and attenuated 6-OHDA-induced reducing of cell total anti-oxidative capacity and increasing in intracellular ROS level.Conclusions: MgSO4 may protect SH-SY5Y cells against 6-OHDA-induced cell injury.Magnesium transporters SLC41A1,NIPA1,MagT1 and CNNM2 associated with the development of PD.