To better understand the extremely halophilic archaeon Halobacterium species NRC-1, we analyzed its soluble proteome by two-dimensional liquid chromatography coupled to electrospray ionization tandem mass spectrometry. A total of 888 unique proteins were identified with a ProteinProphet probability (P) between 0.9 and 1.0. To evaluate the organism's biochemical activities, the proteomics data was subjected to a biological networks analysis using our BMSorter software. This allowed us to examine the proteins expressed in different biomodules and study the interactions between pertinent biomodules. Interestingly, an integrated analysis of the enzymes in the amino acid metabolism and citrate cycle networks suggested up to eight amino acids may be converted to oxaloacetate, fumarate, or oxoglutarate and entered the citrate cycle for energy production. In addition, glutamate and aspartate may be interconverted from other amino acids or synthesized from citrate cycle intermediates in order to meet the high demand for the acidic amino acids that are required to build the organism’s highly acidic proteome. Thus this study demonstrated that proteome analysis can provide useful information and help systems analyses of organisms.