In this thesis, importance of the extracellular matrix protein osteopontin as endogenous marker of hypoxia and therapeutic target in radiotherapy was investigated. In vitro hypoxia resulted in cell type-specific regulation of OPN. In vivo OPN correlated with various hypoxia-induced parameters and OPN is in combination with other hypoxic markersan important prognostic factor for survival. The reduction of gene expression of OPN and OPN splice variants respectively, resulted alone and in combination with radiation respectively, in breast cancer and glioblastoma in inhibition of proliferation, migration and clonogenic survival as well as induction of apoptosis. In breast cancer cells radiosensitization was obtained after reduction of gene expression of OPN under normoxia and hypoxia. In vivo OPN and OPN splice variants were identified as prognostic marker for STS patients, especially for patients with radiotherapy.