Glioblastoma multiforme (GBM) is the most prevalent type of primary malignant brain tumor which has high resistance to chemotherapy. Temozolomide (TMZ) is a chemotherapeutic drug used for treating GBM patients. It is well known that the expression levels of heat shock proteins (HSPs) are generally elevated in various cancer types and they are suitable biomarkers for the therapy. Resveratrol (RSV), a natural polyphenolic molecule, is a potent compound to prevent cancer. In the scope of this study, it was considered that the use of RSV with chemotherapeutic drug TMZ might increase the sensitivity of glioblastoma cells via inhibition of Hsp27 and give positive results for drug efficacy. For this purpose, MTT assay for cell viability, Western blot analysis for Hsp27 and protein carbonyl levels, caspase activity assay for apoptosis, Comet assay for DNA damage and spectrofluorometric analysis for ROS levels were performed in glioma and non-cancerous cells. After optimization of the studies, the doses of 50 mu M TMZ and/or 5 mu M RSV, which is the optimum result for the viability of the cells, was applied for all experiments. It was shown that combined therapy suppressed Hsp27 level and induced apoptosis in U87MG cells. Furthermore, it has shown that there were no negative effects of this combined therapy in HEK-293 cells. These findings showed that the combination of resveratrol and temozolomide provides a feasible strategy to obtain better therapeutic efficacy by avoiding possible toxicity and side effects in healthy cells.