Objective To determine the effects of solid-phase ligand libraries on enrichment of low-abundance serum protein and improve the low-abundance serum protein identification by mass spectrometer(MS).Methods Three pooled serum samples were treated with ProteoMiner and then subjected to one-dimensional (one-D) or two-dimensional (two-D) SDS-PAGE followed by comparative image analysis.The remarkable increased protein spots on two-D map were identified by high performance liquid cbromatogrphy(HPLC) coupled on-line to ESI/MS-MS.Results The one-D and two-D gel map revealed more low-abundance protein bands and protein spots, respectively. MS identification of significantly enriched protein spots on two-D gel improved low-abundance protein identification after library beads treatment, e.g. clusterin, vitronectin, C4b-binding protein alpha chain，complement C4-A. Conclusion The technique of solid-phase ligand libraries can enrich serum low-abundance proteins whilst decrease high-abundance protein concentration, which indicates that this method is useful for enrichment of low-abundance protein and id