In this invention, a biomarker discovery method has been developed using specific biotin-labeled oligonucleotide ligands and magnetic streptavidin beads. In one embodiment, the oligonucleotide ligands are firstly generated by whole-cell based SELEX technique. Such ligands can recognize target cells with high affinity and specificity and can distinguish cells that are closely related to target cells even in patient samples. The targets of these oligonucleotide ligands are significant biomarkers for certain cells. These important biomarkers can be captured by forming complexes with biotin-labeled oligonucleotide ligands and collecting the complexes using magnetic streptavidin beads, whereupon the captured biomarkers are analyzed to identify the biomarkers. Analysis of biomarkers include HPLC-Mass Spectroscopy analysis, polyacrylamide gel electrophoresis, flow cytometry, and the like. The identified biomarkers can be used for pathological diagnosis and therapeutic applications. Using the disclosed methods, highly specific biomarkers of any kinds of cells, in particular cancer cells, can easily be identified without prior knowledge of the existence of such biomarkers.