The ATP binding cassette (ABC) E1 (ABCE1), a member of the ABC family, was originally described as the RNase L inhibitor. Through forming a heterodimer with RNase L, ABCE1 participates in the negative regulation of the 2-5A/RNase L system and thus mediates a wide range of biological functions. Recent evidence has shown the new roles of ABCE1 in tumorigenesis. However, there have been no investigations on the specific effect of ABCE1 on glioma. In the present study, we examined the expression pattern and possible role of ABCE1 in glioma. Our study demonstrated that ABCE1 was up-regulated in glioma tissues and cell lines. Down-regulation of ABCE1 inhibited temozolomide (TMZ) resistance of glioma cells in vitro and in vivo. In addition, we found that the PI3K/Akt/NF-κB pathway was involved in ABCE1-mediated chemoresistance of glioma cells. Taken together, our study suggested ABCE1 as a promising target for glioma chemotherapy.