Septin4, a member of polymerizing GTP-binding proteins family, is reported to be involved in cytoskeletal organization in mitosis, apoptosis, fibrosis, and other cellular processes. Since various Septin4 expression patterns were reported in different diseases, this study aimed to investigate Septin4 expression in human LX-2 cell line stimulated by lipopolysaccharides (LPS) and attempted to clarify the relationship between Septin4 and hepatic inflammatory injury and fibrosis. In this subject, human stellate cell line LX-2 was stimulated by LPS. The expression of Septin4 was analyzed by Western blot and quantitative real-time PCR. To observe the relationship among Toll-like receptor 4 (TLR4), TGF-β, and Septin4, proteins from the anti-TLR4 antibody blocked cells, as well as the TGF-β-induced cells, were analyzed by the method of Western blot. As the results, LPS could induce the alteration of α-smooth muscle actin and Septin4 expression in LX-2 cells. Septin4 expression was regulated by LPS stimulation through TLR4 and TGF-β pathway. These results therefore suggest that Septin4 may be involved in the process of activation of hepatic stellate cells by LPS stimulation. Further work would focus on the function of Septin4 in hepatic inflammatory injury and fibrosis.