Objective To explore the toxic effects of formaldehyde using the human neuroblastoma SH-SY5Y cellline as an in vitro model of nerve cells, and to provide a scientific basis for the mechanism by which formaldehyde damagesneuronal cells. Methods SH-SY5Y neuroblastoma cells were treated with formaldehyde at different concentrations (controlgroup, 0. 05 mmol/ L, 0. 1 mmol/ L, 0. 25 mmol/ L, 0. 5 mmol/ L, and 1 mmol/ L). Cell scratch test, high-powermicroscopy, and CTG cell activity assay were used to detect the effect of formaldehyde on cell migration, morphology, andsurvival, respectively. Flow cytometry was used to detect the effect of formaldehyde on apoptosis, while ultrastructuralchanges were observed by transmission electron microscopy. Expression levels of phosphorylated tau, amyloid β, andmitochondrial fission-associated proteins were detected by western blotting. Results The migratory ability of SH-SY5Ycells was inhibited by even low (0. 05 mmol/ L) concentrations of formaldehyde, and the survival and proliferation of cellswas reduced by 0. 1 mmol/ L for 4 h. These changes were positively correlated with the dosage and duration of formaldehyde.Indeed, 0. 05 mmol/ L formaldehyde could induce the apoptosis and mitochondrial injury in the SH-SYSY cells, whereas,0. 25 mmol/ L formaldehyde increased mitochondrial fission and upregulated the expression level of phosphorylated tauprotein in the neuronal cells. Conclusions Formaldehyde can damage the neuronal cells, as it inhibites cell activity andproliferation of SH-SY5Y cells, reduces their migratory ability, and induces apoptosis. Moreover, formaldehyde upregulates the phosphorylation level of tau protein in neurons.