BACKGROUND Celastrol is extracted from the root of the Chinese traditional herb Tripterygium wilfordii, which has anti-cancer effects in multiple cancers. However, the effect of celastrol on the metastasis of triple-negative breast cancer and its mechanism remain largely unknown. MATERIAL AND METHODS MDA-MB-468 and MDA-MB-231 cells were treated with various doses of celastrol for 24 h. Cell viability was measured via MTT analysis. Cell migration and invasion were detected via transwell analysis. The expression of interleukin-6 (IL-6) was measured after transfection of short-hairpin RNA against IL-6 or celastrol treatment via quantitative real-time polymerase chain reaction, Western blot, or enzyme-linked immunosorbent analysis (ELISA). The protein levels in the nuclear factor-kappaB (NF-kappaB) pathway were measured by Western blot. The interaction between celastrol and NF-kappaB-mediated IL-6 was investigated by luciferase reporter assay. RESULTS High concentrations of celastrol inhibited viability of MDA-MB-468 and MDA-MB-231 cells, but low doses of celastrol showed little effect on cell viability. Low doses of celastrol suppressed cell migration and invasion, and knockdown of IL-6 also repressed cell migration and invasion. Moreover, treatment with celastrol decreased IL-6 expression at mRNA and protein levels. IL-6 overexpression mitigated celastrol-mediated suppression of cell migration and invasion. Additionally, celastrol blocked the NF-kappaB pathway to inhibit IL-6 levels. CONCLUSIONS Celastrol repressed migration and invasion through decreasing IL-6 levels by inactivation of NF-kappaB signaling in triple-negative breast cancer cells, providing a novel basis for use of celastrol in treating triple-negative breast cancer.