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Based on liver cancer model built in SD rats, the contents of trace elements (Cu, Fe, Zn, Ca and Mg), AFP, CEA, SF, TH and IGF-II in serum were measured at different stages to explore the molecular changes during the rat liver cancer development.The SD rat liver cancer model was built by using diethylnitrosamine (DENA) as the mutagen. During 16 weeks of DENA gavage, blood samples were taken in the 14th, 28th, 56th, 77th, 105th and 112th days respectively after the first day of gavage with DENA, then the contents of five trace elements (Cu, Fe, Zn, Ca and Mg), T3, T4, IGF-II, AFP, CEA and SF in serum were determined.During the development of the rat liver cancer, in the test group, the Cu content significantly increased in serum, while the contents of Fe, Zn and Ca significantly decreased. The content of Mg showed no significant change. AFP and CEA of the test group showed same expression level with the control group; while the content of SF was lower than that of the control group when cancerization appeared. T3 and T4 increased at the first stage and then went down, and the content of IGF-II was always high.Cu, Fe, Zn, Ca, T3, T4, SF and IGF-II are closely related to the development of liver cancer. The changes of their contents in the development of cancer could enlighten the researches on cancer pathogenesis and prevention.