MicroRNAs (miRNAs) have been found to play important regulatory roles in certain neurodegenerative diseases. The aim of the present study was to investigate the effect of miRNA‑153 (miR‑153) on the neural differentiation of HT‑22 cells. Overexpression of miR‑153 induced the differentiation of HT‑22 cells, increasing the number of protrusions and branches, reducing the S phase distribution of the cell cycle, and attenuating the cell proliferation rate as determined using the Cell Counting Kit‑8 assay. Furthermore, miR‑153 increased the expression of neuron‑specific γ‑enolase (NSE), neuronal nuclei (NeuN), and N‑ethylmaleimide‑sensitive fusion attachment protein 23 (SNAP23) and SNAP25 at the transcriptional and protein level by PCR and western blot analysis. Moreover, miR‑153 caused obvious upregulation of peroxiredoxin 5 (PRX5), which has been found to protect neural cells from death and apoptosis. miR‑153 promoted neural differentiation and protected neural cells by upregulating the neuron markers γ‑enolase, neuronal nuclei, and the functional proteins SNAP23, SNAP25 and PRX5. Therefore, miR‑153 may be a potential target for the treatment of certain neurodegenerative diseases.