To find the most influential genes which are responsible for Glioblastoma (GBM) the differentially expressed tumorous cells and normal brain cells are explored using Protein–Protein Interaction network, Gene Oncology analysis and pathway analysis. Glioblastoma (GBM) (Kalinina J, Peng J, Ritchie JC, Erwin G, Meir V (2011) Proteomics of gliomas: Initial biomarker discovery and evolution of technology: Neuro Oncology 13(9):926–942. 10.1093/neuonc/nor078) is a very common rapidly-growing and aggressive type of brain tumor which is also classified as a grade IV astrocytoma by WHO, the uppermost grade. It is very crucial to understand the main molecular mechanisms those involve in GBM progression for emergent better diagnostic and treatment approaches because of its very poor post diagnosis survival rate. To completely understand the disease and extend targeted therapies recognition of main genes engaged in GBM pathogenesis is equally necessary. In our study two pair of gene chips GSE108474 and GSE50161as well as GSE12657 and GSE42656, which are collected from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) are analyzed and recognized to compare gene expression between Glioblastoma and normal samples and significantly common up regulated and down regulated genes are identified from each pair of chips. The PPI networks are investigated using the STRING 11.5 where the hub genes are identified from each pair using Cytoscape 3.9.1. Using GO enrichment analysis and KEGG pathway analysis on selected hub genes, the potential and significant genes are identified.