In order to investigate novel biomarkers for the detection of coronary artery disease for effective therapeutic targets, a comprehensive understanding of the protein networks and protein expression abundance in coronary artery samples is required. This was established by means of liquid chromatography (LC)‑mass spectrometry (MS)/MS analysis in the present study. A total of 20 human coronary artery specimens from 2 autopsied adults were employed in the present study. The natural history and histological classification of the atherosclerotic lesions of the coronary artery samples were analyzed by hematoxylin and eosin (H&E) staining, and the human coronary arterial proteome and proteomics features were characterized by MS analysis. The present study identified 2,135 proteins in the 20 coronary artery segments samples from the 2 cases. Combined with the results of H&E staining of the coronary artery samples, a total of 174 proteins, including 4 upregulated proteins and 164 downregulated proteins (excluding 6 proteins with inconsistent expression tendencies), were shown to be associated with coronary artery disease. In addition, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment of the differentially expressed proteins revealed that the mitochondrial energy metabolism may be responsible for the occurrence and development of coronary artery atherosclerosis. The human coronary arterial proteome can be considered as a complex network whose architectural characteristics vary considerably as a function of the presence or absence, and histological classification of coronary artery atherosclerosis. These data thus suggest that the prevention of mitochondrial dysfunction via the retrieval of the mitochondrial associated proteins expression may be a promising target in coronary artery disease.