Breast cancer causes second largest cancer deaths among women globally. Aromatase enzyme and epidermal growth factor receptor (EGFR) act as an important targets for breast cancer therapy. The present study investigates the computational docking interaction of some new chalcones comprising benzimidazole and quinoline against these targets. The docking study of the ligands were carried out against aromatase (PDB ID 3S7S) and EGFR (PDB ID 3POZ) using Schrodinger suite. The dock score shows that the ligands have better binding interaction with the target aromatase than the standard exemestane. The ligand 10A and 15A showed good binding with aromatase whereas ligand 1A bind with EGFR as a better inhibitor. All the compound obeyed Lipinski’s rule of five and can be considered as novel drug targets for breast cancer therapy.