Objective To investigate the effect of Jiawei Simiao powder on the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway through miR-146a in monosodium urate (MSU) crystal-induced RAW264.7 macrophage inflammation models, and to explore its anti-inflammatory mechanism. Methods A cell model of gouty arthritis was established by inducing RAW264.7 cells with MSU crystals. Cells were divided into control, model, Jiawei Simiao powder, and colchicine groups and cell viability was assessed using the CCK-8 method. Levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay. Expression levels of miR-146a miRNA and TLR4, myeloid differentiation factor 88 (MyD88), TNF receptor-associated factor 6 (TRAF6), and NF-κB p65 mRNA were detected by quantitative real-time polymerase chain reaction amplification technology, and protein expression levels of TLR4, MyD88, TRAF6, and phospho (p)-NF-κB p65 were evaluated by Western blot. Results miR-146a expression was significantly decreased in the model group compared with the control group (P<0.01), while mRNA and protein expression levels of TLR4, MyD88, and TRAF6, and protein expression of p-NF-κB p65, IL-1β, IL-6, and TNF-α were significantly increased (P<0.01). In contrast, miR-146a expression was significantly increased (P<0.01) and mRNA and protein expression of TLR4, MyD88, and TRAF6, and p-NF-κB p65 protein expression(P<0.01), as well as IL-1β, IL-6, and TNF-α levels (P<0. 05) were significantly decreased in the Jiawei Simiao powder and colchicine groups. Conclusions Jiawei Simiao powder may alleviate MSU crystal-induced macrophage inflammatory responses by upregulating miR-146a, suppressing TLR4/NF-κB signaling pathway activation, and decreasing secretion of inflammatory factors.