Background and Aim: Glioblastoma multiforme (GBM) are the most aggressive class of cancer of central nervous system with hallmark characteristics that include rampant proliferation, necrosis, and endothelial proliferation. Epidermal growth factor receptor (EGFR) has been implicated as the primary contributor to glioblastoma initiation and succession. The present study was designed to evaluate EGFR protein expression in GBM as predictor of response to therapy and survival. Materials and Methods: Epidermal growth factor receptor was assessed by immunohistochemistry as a percentage of positive tumor cells in hot spots (10 high-power fields). The study group comprised of 35 cases of GBM. All cases underwent surgical resection and subsequently underwent radiotherapy (n = 17) or radiotherapy with adjuvant temozolomide chemotherapy (n = 18). Immediate response to therapy was assessed at 3 months using World Health Organization response evaluation criteria in solid tumors criteria and cases followed up for survival. Results: Twenty-four cases (68.6%) expressed EGFR while 11/35 (31.4%) cases were negative. Response to therapy was evident in 21/35 cases (60.0%) and 14/35 were (40.0%) nonresponders. Mean EGFR protein expression in responders was 37.23 ± 33.70 and in nonresponders was 59.5 ± 39.46 (P = 0.542). The percentage of responders which were EGFR negative was 72.7% and while response in EGFR positive cases was observed in 54.2%. Mean survival in EGFR positive and negative GBM was 394.37 ± 189.11 and 420.54 ± 191.23 days, respectively. Conclusion: The EGFR negative cases appear to respond better to therapy, however, the difference is not statistically significant (P = 0.298). Further, EGFR protein expression does not play a definitive role in predicting survival. This is an original study evaluating EGFR in terms of therapeutic response.