To investigate the relationship between the plasma biomarker proteins and the states of Zang-Fu organs in patients with phlegm or blood stagnation syndromes due to hyperlipidemia and atherosclerosis. The states of Zang-Fu organs in 146 patients with hyperlipidemia and atherosclerosis were diagnosed by syndrome differentiation of traditional Chinese medicine. The plasma proteins from these patients were separated by two-dimensional polyacrylamide gel electrophoresis (2-DE). Differential protein profiling was established by Image Master 6.0 software, and the differential proteins were analyzed by quadrupole time of flight mass spectrometry (Q-TOF-MS). The association between the plasma biomarker proteins and the states of Zang-Fu organs was analyzed by graphical models. The biomarker proteins such as fibrinogen gamma chain, albumin and apolipoprotein AI (precursor) in discrimination of the patients with phlegm syndrome from phlegm accumulating with stagnation syndrome were correlated with the deficiency of kidney-qi, heart-qi and spleen-qi. Among the four biomarker proteins in discrimination of the patients with phlegm syndrome from blood stagnation syndrome, albumin, adrenomedullin binding protein (precursor) and haptoglobin (precursor) were correlated with the deficiency of kidney-qi and heart-qi, but complement component C4 was independent of the deficient Zang-Fu organs. The biomarker albumin was associated with the deficiency of kidney-qi, heart-qi and spleen-qi, and adrenomedullin binding protein (precursor) was correlated with the deficiency of spleen-qi in discrimination of the patients with blood stagnation syndrome from phlegm accumulating with stagnation syndrome. As the potential biomarker proteins in discrimination of the patients with non-phlegm and non-stagnation syndrome from phlegm accumulating with stagnation syndrome, the fibrinogen beta chain was related with the deficiency of kidney-qi, and apolipoprotein AI (precursor) was correlated with both the deficiency of kidney-qi and heart-qi. There exists inherent correlation between the states of Zang-Fu organs and the plasma probable biomarker proteins in the patients with different phlegm or blood stagnation syndromes due to hyperlipidemia and atherosclerosis.