During brain development, the expression of promyelocytic leukemia zinc finger (Plzf) in neural stem cells is precisely controlled to maintain the balance between neural stem cell self-renewal and differentiation. However, the mechanism underlying transcriptional regulation of Plzf in neural stem cell is still unclear. Herein, using P19 embryonal carcinoma cells as a model, we observed that Plzf expression was induced in the P19-derived embryonic bodies, which enrich neural stem-like cell populations, as demonstrated by the expression of neural stem cell markers, Nestin and Sox2. We then characterized the Plzf promoter and identified two E2f1 binding sites (−755/-751 and −53/-49, the transcription start site was designated as +1) are important for the activation of Plzf promoter. Finally, we found that the induction of Plzf in the neural stem-like cells derived from pluripotent P19 cells is decrease by E2f1 knockdown. Taken together, we conclude that E2f1 is an important transcription factor that regulates Plzf transcription and may involve in maintaining the self-renewal ability of neural stem cells. •Plzf expression is induced in the neural stem-like cells derived from pluripotent P19 embryonal carcinoma cells.•E2f1 up-regulates Plzf promoter activity in P19 cells.•Two E2f1 binding sites (−755/-751 and −53/-49) are sufficient for the activation of Plzf promoter.•The induction of Plzf in the neural stem-like cells derived from pluripotent P19 cells is decreased by E2f1 knockdown.