Aim: To investigate whether Nurr1 gene, a member of the nuclear receptor superfamily of transcription factors, contributed to 6-OHDA-induced DAergic neurons insults by comparing the effect of 6-OHDA on neuroblastoma cells SK-N-SH and SK-N-SH cells overexpressing Nurr1 gene (SK-N-SH/Nurr1). Methods: The effect of Nurr1 gene on cell proliferation of SK-N-SH cells was investigated, then SK-N-SH and SK-N-SH/Nurr1 cells were exposed to 6-OHDA (5 -100 μmol · L -1 ) for 1-24 h, cells' morphology was observed under phase-contrast microscope. The cells viability was analyzed via MTT assay. Apoptosis was detected using Hoechst33342 staining. Results: The Nurr1-overexpressing SK-N-SH cells showed significantly slow growth rate compared with that of SK-N-SH cells. Treatment with 50 μmol · L -1 6-OHDA changed SK-N-SH-Nurr1 cells' morphology within 1 h, accompanied by retraction of processes, shrinkage of cell body, whereas the morphology of SK-N-SH cells changed after treated with 50 μmol · L -1 6-OHDA for 2 h. The result of MTT assay indicated that exposure to 100 μmol · L -1 6-OHDA for 24 h induced a significant decrease in SK-N-SH/Nurr1 cells survival compared with SK-N-SH cells at various time points with an IC 50 value of 75 μmol · L-1 and 50 μmol · L -1 respectively in SK-N-SH and SK-N-SH/Nurr1 cells. The evidence that treatment with 75 μmol · L -1 6-OHDA for 12 h induced typical apoptosis in SK-N-SH/Nurr1 cells was found in morphological features provided by Hoechst33342 staining, including chromatin condensation and nuclear fragmentation, and the percentages of apoptosis in SK-N-SH/Nurr1 cells was about 22%-24%. In contrast, no morphological characteristics of apoptosis in SK-N-SH cells were observed. Conclusions: The present study suggests that Nurr1 gene renders SK-N-SH cells more vulnerable to neurotoxic insults. The mechanism of such action is probanly that normal Nurr1 gene function can stimulate apoptotic pathway induced by 6-OHDA, and play a major role in the high sensitivity of DArgic neurons to 6-OHDA insults as a vulnerable factor.