Objective: To explore the mechanism by which Jiawei Simiao Powder regulates the TLR4/NF-κB signaling pathway via miR-146a in MSU crystal-induced RAW264.7 macrophage inflammatory models. Methods: A gouty arthritis model was established by inducing RAW264.7 cells with MSU crystals and divided into control, model, Jiawei Simiao Powder, and colchicine groups. Cell viability was assessed using the CCK-8 method. Levels of IL-1β, IL-6, and TNF-α were measured by ELISA. Expression of miR-146a miRNA and mRNA of TLR4, MyD88, TRAF6, and NF-κB p65 was detected by RT-PCR, while protein expression of TLR4, MyD88, TRAF6, and p-NF-κB p65 was evaluated by Western blot. Results: Compared to the control group, the model group showed significantly decreased miR-146a expression (P<0.01) and increased mRNA and protein expression of TLR4, MyD88, and TRAF6, p-NF-κB p65 protein expression, and levels of IL-1β, IL-6, and TNF-α (P<0.01). In contrast, Jiawei Simiao Powder and colchicine groups exhibited significantly increased miR-146a expression (P<0.01) and decreased mRNA and protein expression of TLR4, MyD88, and TRAF6, as well as reduced p-NF-κB p65 protein expression and levels of IL-1β, IL-6, and TNF-α (P<0.01). Conclusion: Jiawei Simiao Powder may alleviate MSU crystal-induced macrophage inflammatory responses by upregulating miR-146a, inhibiting the activation of the TLR4/NF-κB signaling pathway, and reducing the production of inflammatory factors.