In conclusion, we have shown that (i) YB-1 overexpression promotes EMT features, cell migration, and invasion in breast cancer cell lines; (ii) YB-1 knockdown partially reverts the EMT phenotype of MDA-MB-231 cells; (iii) YB-1 regulates the IL-6/STAT3 pathway by inducing IL-6 de novo synthesis and activity; (iv) IL-6 is required for YB-1–induced acquisition of EMT-like features; (v) IL-6 can activate YBX1 mRNA expression and YB-1 phosphorylation/activation; and (vi) induction of EMT by IL-6 requires YB-1. This evidence concerns the gene STAT3 and breast cancer.