Objective  To explore the effect and mechanism of kaempferol (Kae) on interleukin (IL)-1β-induced inflammatory damage of chondrocytes based on the reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathway.  Methods  SD rats were randomly divided into sham operation(sham) group, osteoarthritis (OA) group and Kae group. The OA model was established by anterior cruciate ligament transection. After 3 weeks of intervention with 2.5 mg/L Kae (100 μl intra-articular injection, once a week), the ROS level and the expression of ROS/TXNIP/NLRP3 pathway proteins in rat cartilage tissue were detected using the 2’,7’-Dichlorodihydrofluorescein diacetate (H2DCFDA) fluorescent probe and Western blotting, respectively. Pathological examination of cartilage tissue was performed using safranin O-fast green staining. Human articular chondrocytes were randomly classified into the control (Ctrl) group, the IL-1β group, the IL-1β+Kae group, the IL-1β+ trimethylamine N-oxide (TMAO) group, and the IL-1β+Kae+TMAO group. After treatment with IL-1β, Kae and ROS activator TMAO, CCK-8 assay and EdU staining were used to detect the cell proliferation. Measured the release of cellular lactate dehydrogenase (LDH). Flow cytometry was used to measure apoptosis. Immunofluorescence staining was used to detect the expression of cell proliferative protein (Ki67). The ratio of Bcl-2 and the expression of collagen type Ⅱ α1 chain (COL2a1) and matrix metalloprotein 13 (MMP13). ELISA was used to determine the release of cellular inflammatory factors. The ROS level and the expression of ROS/TXNIP/NLRP3 pathway proteins of cells were detected using the H2DCFDA fluorescent probe and Western blotting.  Results  Kae alleviated the degeneration and damage of cartilage tissue in OA rats, and reduced their Mankin scores, ROS levels, the relative expression of TXNIP, NLRP3, cysteine-containing aspartate-specific proteases 1 (Caspase-1) and IL-1β proteins (P<0.05). Compared with the Ctrl group, the IL-1β group reduced cell viability, EdU positivity rate, Ki67 and COL2a1 positivity ratios (P<0.05), and increased LDH release, apoptosis rate, Bax/Bcl-2 ratio, MMP13 positivity ratio, tumor necrosis factor-α (TNF-α), IL-6, IL-8 and IL-18 releases, ROS level, TXNIP, NLRP3, Caspase-1 and IL-1β protein relative expression (P<0.05). Kae ameliorated the aforementioned pathological changes in IL-1β induced chondrocytes, whereas TMAO exacerbated these changes. TMAO reversed the mitigating effect of Kae on the inflammatory damage in IL-1β induced chondrocytes.   Conclusion  Kae can reduce IL-1β-induced inflammatory damage to human articular chondrocytes, which may be achieved by inhibiting the activation of the ROS/TXNIP/NLRP3 pathway.