Objective To explore curcumin inhibiting the malignant phenotype of human renal cell carcinoma (RCC) by regulating the Toll⁃like receptor 4/nuclear factor⁃κB (TLR4/NF⁃κB) signaling pathway. Method The HK⁃2, 786⁃0, and ACHN cell lines cultured in vitro were divided into control group, curcumin group, TLR4/NF⁃κB signaling pathway inhibitor group (TAK⁃242 group). The curcumin group was divided into curcumin 10, 20, 40 μmol/L subgroup. CCK⁃8 method, Annexin V⁃FITC/PI staining, scratch test, and Transwell chamber test were used to detect ability of cell proliferation, apoptosis, migration and invasion; ELISA method was used to detect cell interleukin⁃1β (IL⁃1β), interleukin⁃6 (IL⁃6) and tumor necrosis factor⁃α (TNF⁃α) content; Western blotting method was used to detect the expression of TLR4, NF⁃κB p65, B cell lymphoma⁃2 (Bcl⁃2), BCL2⁃Associated X (Bax), and matrix metalloprotein⁃9 (MMP⁃9). Result Curcumin had no toxic effect at concentrations below 40 μmol/L; in renal cancer cell lines 786⁃0 and ACHN, Compared with the control group, curcumin 10, 20, and 40 μmol/L subgroups can significantly inhibit cell proliferation, migration and invasion, and promote cell apoptosis; IL⁃1β, IL⁃6 and TNF⁃α, TLR4, NF⁃κB p65, Bcl⁃2, MMP⁃9 levels decrease, and Bax levels increase, The differences are statistically significant (P<0.05). Conclusion Curcumin can inhibit the proliferation, migration and invasion of renal cancer cells and promote cell apoptosis by inhibiting the TLR4/NF⁃κB signaling pathway.