Based on PPI network analysis and topological parameter calculation results of four methods, 16 differential proteins were considered as hub proteins of the PPI network of MetS, including 10 up-regulated proteins (Hmgcs1, Fdps, Acat2, Mvd, Hsd17b7, Cyp2c7, Got1, Ass1, Cps1, Cth) and 6 down-regulated proteins (Cyp3a18, Cyp2b2, Cyp7a1, Ugt1a1, Ugt2b7, Aldh1a1), mainly involved in metabolisms of amino acid and cholesterol, especially for Cyp7a1 and Got1 with top degree in PPI network, which may be considered as potential targets for prevention and treatment of MetS. This evidence concerns the gene HMGCS1 and metabolic syndrome.