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Triphenyl phosphate (TPhP) is one of the novel alternative retardants with increasing utility. As a potential obesogen, the direct disruption of TPhP on lipid metabolism in hepatocyte has been widely studied. However, the microRNAs (miRNAs) regulation patterns of lipid metabolism disruption effects in hepatocyte under TPhP exposure remain unknown. This study aimed to elucidate the adverse effect of TPhP on hepatocyte through cell viability, TPhP clearance, and epigenetic miRNA alterations of hepatocytes at short (3 h) and long term (48 h) exposures to TPhP. The cell viability of hepatocyte raised at the low TPhP concentration treatments but dramatically decreased after the 10 µg⋅mL-1 TPhP treatment, and concentration for 50% of maximal inhibitory effect was 46.7 µmol⋅L-1 . The clearance rates of TPhP in hepatocyte were 73.9% and 85.1% after 3 h and 48 h incubations, respectively. Plenty of miRNAs were differentially expressed under TPhP treatments of 5 µg⋅mL-1. The predicted target genes of these differential expressed miRNAs were mainly involved in metabolic, fatty acid biosynthesis, steroid biosynthesis and cancer related pathways. The regulation network of miRNA-mRNA was constructed according to the correlations between miR-34c-5p, miR-301a-5p, and miR-7 and lipid metabolism related genes. Lipid metabolism disruption by TPhP was achieved by a proposed integration network of differential expressed mRNAs and miRNAs. Our study provides important insight in potential miRNAs biomarkers such as miR-4484 and miR-7 and the miRNA-mediated lipid metabolism disruption effect on human hepatocytes under TPhP treatment. [ABSTRACT FROM AUTHOR]