Breast cancer is the most common cause of death among women. Hence discovery of novel molecules to inhibit the breast cancer protein is critical research. Molecular docking, an in-silico techniques been used for the identification of protein-ligand interactions for the current study on breast cancer. Autodock, the common and accurate software for molecular docking was used in the current study. In this study, two compounds 5 α, 8 α-epidioxy-24 ε-methylcholesta-6,22-dien-3 β-ol and Ergosta-5,7,22-trien-3 β-ol from the mushroom Lentinus tuberregium was docked with breast cancer biomarkers like VEGFR2, Human Estrogen Receptor, IL17A and PI3K. Among them Ergosta-5,7,22-trien-3β-ol showed least binding energy of -8.94 kcal/mol against VEGFR2, followed by 6.78 kcal/mol against IL17A, -6.52 kcal/mol against human estrogen receptor and -4.79 kcal/mol against PI3K. The other ligand 5 α, 8 α-epidioxy-24 ε-methylcholesta-6,22-dien-3 β-ol was also found to be potential inhibitor with a binding energies of -6.99 kcal.mol, -6.22 kcal/mol, -6.06 kcal/mol and -3.61 kcal/mol against human estrogen receptor, VEGFR2, IL17A and PI3K respectively. The control drug Abemaciclib, showed a binding energies higher than the ligands. In addition, ADMET studies also revealed that the ligands are safer and no toxic effects. From this current study, the reported ligands from mushroom can be potential and novel inhibitors for drug targets of breast cancer and can be used for the treatment of breast cancer.