Cancer is one of the leading causes of mortality across the globe and is a growing public health issue. Existing agents used in treatment of cancer are known for serious undesirable effects. Hence there is urgent need for new anticancer drugs. In the present work, molecular docking analyses of a few chalcones into the ligand binding domain of epidermal growth factor receptor is reported. The 3D structures of all the 15 designed chalcone derivatives were sketched using chemsketch and geometric optimization with 1000 iterations was carried out using universal force field in Argus Lab until each ligand converged to lowest energy state and saved in .pdb format for docking process. Receptor (Epidermal Growth Factor Receptor tyrosine kinase domain with 4-anilinoquinazoline inhibitor Erlotinib) Pdb-id: 1M17 was undertaken for the analyses. Molecular modeling and docking approaches have been implemented to compare the binding efficiency of the indigenous inhibitor Erlotinib and the designed 15 chalcone derivatives with EGFR kinase.