Finally, we revealed that silencing HPSE curbed the proliferation and metastasis of glioma in mice.<h4>Conclusion</h4>Hypoxia-induced activation of HIF-1α/IL-1β axis in microglia promoted glioma progression via NF-κB-mediated upregulation of HPSE expression. Here, NFKB1 is linked to central nervous system cancer.