The presence of glioma stem cells (GSCs) is thought to be a key factor responsible for development of the incurable glioblastoma multiforme (GBM). GSCs are often displayed during chemotherapy resistance， except for demethoxycurcumin (DMC)， a component of curcumin， which has been previously confirmed to inhibit GSCs proliferation and induce apoptosis. The objective of this study was to identify the main mechanism underlying anti-GSCs resistance by DMC. qRT-PCR was used to determine the expression of miR-145 in glioma patients and GSCs， and GSCs were transfected with miR-145 overexpressed vectors. Then， functional analyses (in vitro and in vivo) were performed to confirm the role of miR-145 and DMC in GSCs. Finally， related proteins were tested by immunohistochemistry and Western blot. miR-145 was atypically low-expressed miRNA in GSCs， and could enhance GSC chemosensitivity to DMC both in vitro and in vivo. Upregulation of miR-145 in GSCs resulted in increased cell growth inhibition and apoptosis to DMC. Further research on the mechanism demonstrated that the combined effects of miR-145 and DMC were involved in the miR-145/SOX2-Wnt/β-catenin pathway. Overexpression of SOX2 reduced GSC resistance to growth inhibition by miR-145+?DMC treatment. ?Our data strongly support an important role for miR-145 in enhancing GSC chemosensitivity to DMC by targeting the SOX2-Wnt/β-catenin axis.