Cerium (Ce) was shown to cause various toxic effects both in rats and mice; however, the molecular mechanism by which Ce exert theirs toxicity is still understood. In this report, the impairment of liver DNA conformation and liver apoptosis of mice caused by CeCl(3) was studied in vivo using inductively coupled plasma-mass spectrometry, various spectral methods, gel electrophoresis, and transmission electron micrograph. We found that the coefficients of liver to body weight of the mice treated with CeCl(3) were significantly increased. Ce(3+) could be significantly accumulated in the liver, and it insert itself into DNA base pairs and/or bind to DNA nucleotide, and alter the conformation of DNA. Furthermore, the evaluation by gel electrophoresis and transmission electron micrograph showed that higher dose of Ce(3+) could cause DNA cleavage and hepatocyte apoptosis in mice. Therefore, our study aroused the attention of Ce application and exposure effects especially on human liver for long-term and low-dose treatment.