The Mass spectrometry (MS)-based blood plasma or serum proteome analysis is limited by interference from albumin, immunoglobins and other commonly abundant proteins. We have found that polyethylene glycol (PEG) can efficiently precipitate immunoglobins while leave albumin largely in the supernatant. By PEG precipitation followed by albumin depletion, an increased number of proteins and N-glycoproteins can be identified by LC-MS/MS from the plasma. In-depth LC-LC-MS/MS proteomic analyses of the plasma and its four fractionated samples (10% and further 20% PEG-precipitated pellets and their supernatants with albumin depletion) have identified 2943, 2242, 3162, 2187 and 2028 proteins respectively, yielding 5040 proteins in total. Therefore, PEG precipitation followed by albumin depletion should be used as a general strategy to expand the MS-based plasma proteome coverage for blood biomarker discoveries; and our datasets in this study provide as resources for increased chances of detecting proteins of interests in the whole plasma or particular fractions.