We have invented a method that can reveal the binding strength and binding specificity of drug molecules interacting with their targets. The molecular system consists of a surface-immobilized DNA and its complementary DNA strands or proteins, or a surface-immobilized receptor protein and its ligand, in the presence or absence of the label-free drug molecule. The binding forces of the DNA duplex, DNA-protein complex, or receptor-ligand pair are measured. The difference of the binding forces with and without the drug molecule quantifies the binding strength and selectivity of the drug molecule to the targeted molecular system. This invention shows for the first time that binding force can serve as a critical and quantitative parameter for drug screening. In addition, this method is efficient, reliable, and inexpensive.