Quercetin, a plant-derived flavonoid, is known for its antitumor and antiproliferative activities. Glioblastoma multiforme (GBM), as a highly aggressive cerebrum tumor, has a poor prognosis that is approximately 12 months despite standard therapy. Therefore, because of the low effectiveness of the current therapeutic strategies, additional medications in combination with chemotherapy and radiotherapy are needed, which could improve the prognosis of GBM patients. Multiple lines of evidence have shown that quercetin regulates many proteins involved in the cellular signal transduction in GBM. In this review, recent findings on the targeting of particular signaling pathways by quercetin and the subsequent effect on the pathogenesis of GBM are presented and discussed.