Nuclear factor -light-chain-enhancer of B cells (NF-B) is one of the most important tumorigenic factors. Although it has been established that NF-B is overly activated in human glioma cells, the molecular mechanisms that lead to the signal transduction to NF-B and thereby the induction of resistance to apoptosis remain poorly understood. The present study demonstrated that mRNA and protein levels of E3 ubiquitin-protein ligase 2 (MIB2) were markedly upregulated in glioma cell lines and clinical samples. Immunohistochemical analysis also revealed high levels of MIB2 expression in glioma specimens. Ectopic overexpression of MIB2 was established in glioma cell lines to investigate its fundamental roles in the response of human glioma to apoptotic inducers. The results indicated that ultraviolet irradiation-induced cell apoptosis was inhibited with MIB2 overexpression in glioma cells. Notably, knockdown of MIB2 using RNA interference was able to increase the sensitivity of glioma cells to the pro-apoptotic agents. The present study identified that MIB2 induces NF-B activation and facilitates the resistance of glioma cell to apoptosis. It was proposed that MIB2 may not only be an important hallmark to glioma disease progression, but that it may also offer novel clinical strategies to overcome resistance to cancer therapies.