Inducing the differentiation of glioma cells into neuron-like cells may be an effective strategy to combat glioma. The histone deacetylase 1/RE-1 silencing transcription factor (HDAC1/REST) complex regulates the expression of multiple neuronal genes. In this study, we analyzed the presence and significance of this regulatory effect in glioma based on bioinformatics methods. The Human Protein Atlas database was used to obtain immunohistochemical staining images. The Gene Expression Profiling Interactive Analysis and Chinese Glioma Genome Atlas databases were used to analyze the expression of HDAC1/REST and neuronal markers in glioma, their effects on survival, and the association between HDAC1/REST and the expression of neuronal markers and stem cell markers. The differentially expressed genes between the high and low HDAC1/REST groups were explored. The Database for Annotation, Visualization and Integrated Discovery database was used for gene ontology and kyoto encyclopedia of genes and genomes pathway enrichment analysis. The results showed that the expression of HDAC1 and REST increased with the grade of glioma, while the expression of neuronal markers decreased with the grade of glioma. High expression of HDAC1/REST and low expression of neuronal markers were associated with poor prognosis. HDAC1/REST expression was negatively correlated with the expression of neuronal markers, and positively correlated with the expression of neural stem cell markers. The genes up-regulated in the high HDAC1/REST group were mainly related to extracellular matrix and inflammation, and the down-regulated genes were mainly related to synapsis. This study suggested that HDAC1/REST may be involved in maintaining the malignant phenotype of glioma cells and the stem cell status of glioma stem cells by inhibiting the expression of neuronal markers, which promote the progression of glioma. [ABSTRACT FROM AUTHOR]