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Perfluorooctanoic acid (PFOA) is one of the most important synthesized perfluorinated compounds, which has ubiquitously contaminated our environment due to its common usage in industry and in daily life. Liver is the major human organ where PFOA is accumulated after the exposure. In view of the various possible toxicities and the unclear toxic effect in liver, this present systematically studied the toxic effects of PFOA on normal human hepatocyte L-02 from three levels: i.e., the regulation of gene transcription (epigenetic toxicity on DNA methylation), transcriptome (mRNA profile) and metabolome: (1) The global DNA methylation alteration and the expression changes of the three DNA methyltransferase genes in the cells were analyzed.