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Objective To investigate the effect and underlying mechanism of artesunate (AS) on the expression of interleukin-6 (IL-6) in mouse primary hepatocytes induced by conjugate bile acids. Methods Mouse hepatocytes were isolated and primarily cultured, and then treated with 25 μmol/L conjugated bile acids. CCK-8 assay was used to determine the toxic effects of AS on the liver cells. The mRNA level of IL-6 in the cells was measured by RT-qPCR, and the protein levels of IL-6, p-65 and phosphorylated-p65 (p-p65) were determined by Western blotting. Results Conjugated bile acids of 25 μmol/L significantly promoted the expression of IL-6 at mRNA and protein levels in mouse primary hepatocytes, while, AS reduced the taurocholic acid (TCA)-induced phosphorylation of p65 and IL-6 level. Further studies revealed that AS suppressed the IL-6 expression through inhibiting p-p65 signaling pathway in mouse primary hepatocytes. Conclusion AS reduces IL-6 expression in mouse primary hepatocytes induced by conjugate bile acids via inhibiting the p-p65 signaling pathway.