The most common malignant brain tumor is Glioblastoma. There are 18000 people newly diagnosed as primary malignant brain tumor in United States, and 50-60% patients are Glioblastoma multiforme (GBM). Gliomas are divided into 4 grades. Glioblastoma Multiforme belongs to grade 4 and the 5 year survival rate is less than 5%. The current managements are surgical treatment, concurrent chemoradiation therapy, and stereotactic radiosurgery. Advances in treatment have been very poorly, significant improvement in survival has been lacking for many years and prognosis not very well. Despite total surgical resections and currently available radio-chemotherapy, malignant gliomas inevitably recur due to reservoirs of notoriously invasive tumor cells that infiltrate adjacent and nonadjacent areas of normal brain parenchyma. Even thought, long-term using of temozolomide can also lead to resistance of this drug and tumor recurrence. The mandatory work is to find out new ways to control tumor. We have an idea that if we can enhance the methylation of the promoter of MGMT gene. Tumor killing and tumor control will be effective and extended. Curcumin has been using on breast Ca and skin Ca control via activating apoptosis of tumor cells. We are also interested whether curcumin can enhance methylation or inhibit tumor growth. In our study, Curcumin combined with temozolomide can promote the killing effect on tumor cells and induce autophagy of tumor cells. Furthermore, we found the cascade of autophage is to increase the activity of AMPK and lead to downstream protein (mTOR) deactivated. Then the amount of LC3-II protein will increase. In conclusion, scientists are interested in autophagy for tumor killing and tumor control. Many reports point out that atuophagy and methylation of MGMT plays an important role in cancer treatment. Curcumin combined with TMZ can induce autophagy of tumor cells. It might be an effective way to against GBM.