Abstract: Glioblastoma multiforme (GBM) is the most common and most malignant primary intracranial tumor in adults, accounting for about 30% to 50% of cranial tumors, with the recurrence rate ranking first in intracranial tumors and currently still no effective treatment.Though its etiology and pathogenesis are still not fully understood, there is increasing evidence that dysfunction of the ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) is involved in the development and progression of GBM.Besides, the interaction between the two regulatory pathways promotes the occurrence and drug resistance of GBM, so both may be potential therapeutic targets of GBM.However, despite significant advances in the understanding of the physiological and pathophysiological roles of UPS and ALP in GBM, the drug development and clinical application of UPS and ALP inhibitors still remain challenging.In this paper, the recent progress of research on the role of UPS and ALP in GBM are reviewed, and the latest development of drugs targeting UPS and ALP for the treatment of GBM are further discussed, so as to provide potential targets and more therapeutic options for GBM.