Objective To explore the mechanism of Tadehaginoside in regulating the NF-κB/NLRP3/Caspase-1 signaling pathway and inhibiting hepatic stellate cell activation.Methods An in vitro cell model of human hepatic stellate cell LX-2 was developed, and using CCK-8 method to detect the effect of Tadehaginoside on LX-2 proliferation. Randomly divide LX-2 cells in logarithmic growth phase into 5 groups: a blank control group, a TGF-β₁ activation group, a TGF-β₁+Tadehaginoside low-dose group, a TGF-β₁+Tadehaginoside medium-dose group, and a TGF-β₁+Tadehaginoside high-dose group. All other groups except for the blank group were added to a culture medium containing TGF-β₁ (final concentration of 5 μg/L) to promote proliferation and activation for 24 hours. Then, low, medium, and high-dose Tadehaginoside groups (final concentrations of 20 μg/mL, 40 μg/mL, and 80 μg/mL) were added for intervention. The CCK-8 method was used to detect the effect of Tadehaginoside on LX-2 proliferation. ELISA method detected the expression levels of IL-1β, IL-18, IL-6, and INF-α in the cell supernatant. qRT-PCR and Western blot were used to detect the mRNA and protein expression levels of NF-κB, NLRP3, and Caspase-1 in cells.Results Tadehaginoside can significantly inhibit the proliferation of LX-2 cells. Compared with the blank group, the TGF-β₁ activation group significantly increased the expression levels of IL-1β, IL-18, IL-6, and INF-α in the cell supernatant, as well as the mRNA and protein expression levels of NF-κB, NLRP3, and Caspase-1 in the cells, with statistical differences (P < 0.05). After intervention with Tadehaginoside, compared with the TGF-β₁ activation group, various doses of Tadehaginoside could reduce the expression levels of IL-1β, IL-18, IL-6, and INF-α in cell supernatant and downregulate the mRNA and protein expression of NF-κB, NLRP3, and Caspase-1 in cells, with statistical differences (P < 0.05).Conclusions Tadehaginoside can significantly inhibit the proliferation and activation of hepatic stellate cells, and its mechanism may be related to the regulation of the NF-κB/NLRP3/Caspase-1 signaling pathway.