Aim:The resistance to chemotherapy is a significant clinical issue in recurrent glioma. Chemotherapy such as temozolomide is used for glioblastoma multiforme (GBM) treatment. However, the medical diagnosis of patients with GBM is lower than expected and its recurrence rate is high. The research on targeted therapies based on novel molecular markers for GBM patients is important. The molecular chaperone Glucose-regulated protein 78 kda (GRP78) is overexpressed in various tumors and in the endoplasmic reticulum. Material and Methods:Western blot analysis and real-time PCR were done to detect the expression of GRP78 in GBM tissues.Results:It was detected that GRP78 is up-expressed in GBM, especially in recurrent GBM. And relapsed patients undergoing radiotherapy (RT) plus temozolomide chemotherapy after primary tumor removal induces C/EBP homologous protein (CHOP). Conclusion:Results mentioned-above illustrate an essential function of GRP78 in the pathogenesis of GBM and regard this receptor as a latest prognostic marker for further GRP78-targeted molecular cancer therapy and potential diagnosis of GMB.