Glioblastoma is a malignant tumor of the central nervous system with poor prognosis and has the features of difficult surgical resection， high invasiveness and proliferation， and strong drug resistance. Endoplasmic reticulum stress （ERS） disrupts the homeostasis of other proteins in cells and thus leads to the activation of unfolded protein response （UPR）， which is essential to the restoration of this balance and cell survival. Except as an adaptive response， UPR is also associated with tumorigenesis. Hypoxia， reactive oxygen species， and deprivation of nutrients in tumor microenvironment are the well-known predisposing factors for UPR. This article reviews the current understanding of UPR in adults with the most life-threatening disease glioblastoma multiforme （GBM）. Chronic activation of UPR is observed in the samples of patients， and standard chemotherapy and radiotherapy can lead to cell death partially by aggravating ERS. UPR is associated with increased sensitivity of apoptosis inducers such as TRAIL and MDA-7. Finally， ERS is considered associated with the maintenance of homeostasis in GBM stem cells. The role of IRE1 and PERK sensors in UPR in the mouse model of GBM has been reported， while further studies are still needed to investigate their direct roles. In summary， UPR may become a promising target for new therapeutic interventions for GBM by inhibiting its activity.