To study the serum proteomes of essential hypertension (EH) patients with abundant phlegm-dampness, and try to find special proteins associated with abundant phlegm-dampness syndrome. Fifty-nine hypertension patients were included, and the patients were divided into abundant phlegm-dampness syndrome group (39 cases) and non-phlegm-dampness syndrome group (20 cases). To find the special proteins associated with abundant phlegm-dampness, the EH patients with non-phlegm-dampness and another 30 healthy persons were regarded as control. Weak cation nano-magnetic beads were used to capture proteins in serum, and proteomic fingerprint was made by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). All the proteomic fingerprints were analyzed by Biomarker Wizard 3.1 Software. Then Biomarker Patterns Software (BPS) 5.0 was used to identify the differentiated proteins, which could induce phlegm-dampness. There were 102 differentiated protein peaks between abundant phlegm-dampness and the control group. The best markers of abundant phlegm-dampness were protein peaks with the mass to charge ratio (m/z) of 9,334.958 m/z (the expression increased), 9,280.191 m/z (the expression decreased), 8,030.794 m/z (the expression increased), and 2,941.551 m/z (the expression increased). These four protein peaks found by BPS could induce abundant phlegm-dampness. They could be used to separate the abundant phlegm-dampness syndrome from the healthy persons and the hypertension patients with non-phlegm-dampness. The sensitivity of the model was 93.103% (27/29), specificity was 92% (23/25), false positive rate was 8% (2/25), false negative rate was 6.897% (2/29) and Youden's index was 85.103%. Blind test data indicated a sensitivity of 90% (9/10) and a specificity of 88% (22/25), and the false positive rate was 12% (3/25), false negative rate was 10% (1/10), and Youden's index was 78%. The differentiated proteins between the abundant phlegm-dampness group and the control group are the material foundation of abundant phlegm-dampness. The selected differentiated proteins can be used to distinguish the EH patients with abundant phlegm-dampness from the healthy persons and the EH patients with non-phlegm-dampness. The molecular biology diagnosis model can offer an objective and accurate way for TCM syndrome differentiation.