Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by genetic instability, intratumoral histopathological variability, and unpredictable clinical behavior. Malignant gliomas express preferentially a number of surface markers that may be exploited as therapeutic targets, such as tenascin-C, an extracellular matrix glycoprotein contributes to tumor cell adhesion, invasion, migration and proliferation. Disappointing results in the treatment of gliomas with surgery, radiation and chemotherapy have fuelled a search for new treatment modalities. Here we present the data for 46 patients suffering from brain tumor. They were resected and treated with dsRNA (ATN-RNA) complementary to the sequence of tenascin-C mRNA. MRI and CT follow up studies showed growth tumor delay or lack of its recurrence symptoms, due to inhibition of TN-C synthesis. A significant improvement in overall survival (OS) was observed without loosing of the quality of life (QOL) of patients. This novel therapy based on RNA interference shows a big therapeutical potential. To our knowledge intervention with RNAi (iRNAi) is the first protocol of application of RNAi in human disease treatment.