Abstract: OBJECTIVE  To study the effects and mechanism of baicalin on high fat-induced lipid accumulation in HepG2 cells.METHODS   HepG2 cells were induced in vitro with 0.75 mmol/L free fatty acid for 24 h to establish an in vitro fat deposition model. The cells were then divided into the following groups; normal group, model group, 50 μmol/L baicalin group, 100 μmol/L baicalin group and 200 μmol/L baicalin group. Oil Red O staining and GPO-PAP enzymatic method were used to detect the changes of TG content in each group of cells, and enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory factors in the supernatant of each group: TNF-α, IL-6. Western Blot was used to detect the following protein content: SIRT1, ChREBP, SREBP1c, FAS Protein.RESULTS   Free fatty acid induced lipid accumulation in HepG2 cells increased, the concentration of TG in cells increased significantly; after the drug intervention, the intracellular lipid droplets in the three drug groups were reduced in comparison to the model group, therefore, showing drug-concentration-dependent results; the TG concentration showed a downward trend in the drug-groups, in which, the differences between the 100 μmol/L and 200 μmol/L drug group and the model group were statistically significant (P < 0.05). Western blot detection showed that compared with the normal group, the expression of SIRT1 protein in the model group was significantly reduced, and the protein expressions of SREBP-1c and FAS increased significantly; the SIRT1 protein expressions of the cells in the 100 μmol/L baicalin group and 200 μmol/L baicalin group increased significantly, while SREBP-1c, ChREBP and FAS protein expression decreased significantly (P < 0.05).CONCLUSION  Baicalin can reduce the lipid accumulation of HepG2 cells induced by free fatty acids and reduce the TG content in the cells. The mechanism may be related to the SIRT1/SREBP-1c pathway.