Transcriptional factors (TFs) are key regulators in orchestrating gene transcription during cancer development. However, their roles in glioma remain elusive. Here, we analyzed the differential expression of TFs and identified ZNF436 is upregulated in glioblastoma and Lower Grade Glioma patients. High expression of ZNF436 is positively associated with poor overall survival and regulated by CREB1 in glioma cells. Knockdown of ZNF436 significantly abolished glioma cells proliferation in vitro. RNA sequencing revealed that ZNF436 regulates cell cycle and controlling BCL10 expression. Over expression of BCL10 promoted glioma cells growth and rescued the malignant behavior in ZNF436-knockdown cells. High levels of BCL10 also result in a worse prognosis in glioma patients. Taken together, our findings identify the CREB1/ZNF436/BCL10 axis represents a novel, potential therapeutic target for glioma interventions. (C) 2019 Elsevier Inc. All rights reserved.