Arene Ru(II) complexes have long been extensively studied as potential inhibitors against the proliferation of tumor cells, but their behavior against the migration and invasion of tumor cells needs further research. In this work, a series of arene Ru(II) complexes, (η6-C6H6)Ru(p-XPIP)Cl]Cl (X = H, 1; F, 2; Cl, 3; Br, 4; and I, 5), have been synthesized, and their inhibitory activity against the migration and invasion of MDA-MB-231 breast cancer cells have been investigated. It is found that all of these complexes exhibit excellent inhibitory activity (IC50) against the growth of MDA-MB-231 breast cancer cells, and the value of IC50 for 1, 2, 3, 4, and 5 is about >300, 52.6, 11.4, 45.5, and 59.1 μM, respectively. Further studies by wound-healing assay, FITC-geltain assay, and flow cytometry assay showed that 3 can apparently suppress the migration and invasion of MDA-MB-231 cells via the joint action of S-phase arrest and apoptosis. Moreover, the binding behavior of these arene Ru(II) complexes with c-myc...