Abstract: Objective To investigate the roles of P53/P21 during neuronal differentiation with a differentiated model of PC12 cells. Methods A new cell line PC12(P53/m175) was created by stable transfection of a retrovirus plasmid pBabe-P53/m175, which contains a dominant-negative P53 gene mutant. After NGF treatment, observing with phase-contrast microscopy, flow cytometric analysis and western blotting of P53 and P21 were performed to compare with the control group. Results Expression of P53 and P21 was obviously increased in NGF-induced PC12 cells. The appearance of cell cycle G1 phase arrest paralleled the increased expressions of P53 and P21. The level of P21 protein did not change after treatment with NGF in PC12(P53/m175) cells and the extent of G1 phase arrest markedly decreased by contrast with the control group. However, we could observe the normal neurite outgrowth in NGF-treated PC12(P53/m175) cells. Conclusion NGF-induced the increased protein levels of P53 and its transcriptional element, P21 is essential for cell cycle G1 phase arrest, but does not necessarily exclusively correlate with the neurite outgrowth of PC12 cells.