Objective To investigate the impacts of liquiritigenin (LQ) on high glucose (HG)-induced inflammatory response and fibrosis in glomerular mesangial cells by regulating Hippo/Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) pathway. Methods HBZY-1 cells were grouped into control group (Ct group), high glucose group (HG group), low-dose LQ group (LQ-L group, 20 μmmol/L), high-dose LQ group (LQ-H group, 40 μmmol/L), pcDNA3.1 group (transfected pcDNA3.1), pcDNA3.1-YAP/TAZ group (transfected pcDNA3.1-YAP/TAZ), LQ-H+ pcDNA3.1 group (40 μmmol/L+ transfected pcDNA3.1), and LQ-H+ pcDNA3.1-YAP/TAZ group (40 μmmol/L+transfected pcDNA3.1-YAP/TAZ).The transfection effect was detected by qRT-PCR and western blot. Cell proliferation was detected by CCK-8 assay. The levels of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and interleukin-1β (IL-1β) in the cell supernatant were measured by ELISA. The protein expressions of collagen IV (Collagen IV) and fibronectin (FN) were measured by immunofluorescence. The protein expressions of connective tissue growth factor (CTGF), transforming growth factor-β1 (TGF-β1), YAP1 and TAZ were measured by western blot. Results HBZY-1 cells successfully overexpressed YAP1/TAZ. Compared with the Ct group, the OD450 value, TNF-α, MCP-1, IL-1β, Collagen IV, FN protein relative fluorescence intensity, CTGF, TGF-β1, YAP1, TAZ protein expressions in HBZY-1 cells in HG group increased (P＜0.05). Compared with the HG group, the OD450 value, TNF-α, MCP-1, IL-1β, Collagen IV, FN protein relative fluorescence intensity, CTGF, TGF-β1, YAP1, TAZ protein expression decreased in LQ-L group and LQ-H group (P<0.05). Compared with HG group and pcDNA3.1 group, the OD450 value, TNF-α, MCP-1, IL-1β, Collagen IV, FN protein relative fluorescence intensity, CTGF, TGF-β1, YAP1, TAZ protein expression in pcDNA3.1-YAP/TAZ group increased (P<0.05). pcDNA3.1-YAP/TAZ attenuated the inhibitory effects of high-dose LQ on HG-induced inflammatory response and fibrosis in HBZY-1 cells. Conclusion LQ may inhibit the HG-induced inflammatory response and fibrosis in HBZY-1 cells by inhibiting the Hippo/YAP/TAZ pathway