Glioblastoma multiforme (GBM) is a primary form of brain tumor with devastating outcomes and very poor overall survival time of about 15 months. Temozolomide (TMZ) is the first choice of chemotherapeutic drug to treat such tumors. The main challenge remains resistance development against TMZ. Resistance causes the treatment to fail in more than 50% of the patient population. Several efforts are made by scientists to overcome TMZ failure, e.g. by using other adjuvant therapeutics. The present work aims at studying proteins that are dysregulated upon TMZ resistance in GBM. Here, the technique used to study proteins and their concentration changes with utmost accuracy and reproducibility is liquid chromatography/mass spectrometry (LC-MS) based proteomics. This technique was used at the sub cellular level to study the roles of proteins in sustaining TMZ resistance in GBM cell line LN-18. Control GBM cells (CTRL) were studied against TMZ-resistant (TMZR) GBM cells. Three subcellular fractions were studied for each of CTRL and TMZR: cytosol, mitochondria and plasma membrane. The extraction method used was efficient enough for crude enrichment however not 100% efficient as some proteins were found in more than one fraction. This could also result from translocation of proteins due to cellular stress response. Each subcellular study is described in a different chapter with discussion on relative protein concentrations seen as dysregulation, protein-protein interactions and functional biology. The detailed analyses presented in this thesis constitute a good basis to study potential biomarkers in more detail for the process of understanding TMZ resistance in GBM.