The development and progression of tumour cells are solely and utterly dependent on the phenomenon of angiogenesis to furnish the necessary supply of oxygen and nutrients and waste removal mechanisms to tumour cells. The phenomenon of tumour angiogenesis itself results from the over-expression of various receptor tyrosine kinases like EGFR, VEGFR, PDGFR, FGFR, etc. EGFR tyrosine kinase is involved in the growth, development, proliferation, and metastasis of various cancers, including ovarian cancer, NSCLC, head and neck cancer, brain cancer and breast cancer. There are different tumour angiogenic pathways associated with the expression of EGFR tyrosine kinase, including the RAS-RAF-MEK-ERK-MAPK pathway, PI3K-AKT pathway and PLC-Ƴ –PKC pathway that result in the growth, proliferation, progression, and metastasis of tumour cells. To date, tremendous research has focussed on the development of safe therapeutic strategies against tumors but the acquired mutational resistance to existing drugs, persistent drug side effects, and low efficacy with therapeutic longevity of drugs compels us to identify novel potential anti-EGFR leads with good efficacy and minimal side effects. In this study, we aimed at developing and designing novel quinazoline based derivatives as an EGFR antagonist to inhibit tumor angiogenesis phenomenon. With the aid of in silico structure-based virtual screening, molecular docking, and MD simulation approaches, we identified the top three leads viz. QU524 (CID:46916170), QU571 (CID:44968219) and QU297 (CID:70702306) as the potential anti-EGFR compounds possessing higher binding energy of -8.64 kcal/mol, -8.24 kcal/mol -8.10 kcal/mol, respectively compared to control drug, erlotinib with binding energy of -7.72 kcal/mol. The above selected leads also cleared ADME, toxicity, metabolic reactivity and cardiotoxicity profile filters. Based on the good binding affinity, pharmacokinetic profiling and stability of the bound complexes we propose the selected leads as prominent EGFR inhibitors to halt the phenomenon of tumor angiogenesis.