•Five Ru complexes bearing 4-anilinoquinazolines were synthesised and characterised.•A RuII complex was characterised crystallographically.•Three Ru complexes exhibit highly inhibitory potential towards EGFR.•A RuIII complex exhibits EGF-dependent antiproliferative activity against MCF-7.•The RuIII complex is more active to induce early-stage apoptosis than gefitinib.The ruthenium DMSO complexes cis-RuIIC12(DMSO)4 and [(DMSO)2H][trans-RuIIICl4(DMSO)2] reacted with 4-(3′-chloro-4′-fluoroanilino)-6-(2-(2-aminoethyl)aminoethoxy)-7-methoxyquinazoline (L1), 4-(3′-chloro-4′-fluoroanilino)-6-(2-(1H-imidazol-1-yl)ethoxy)-7-methoxy quinazoline (L2), N-(benzo[d]imidazol-4-yl)-6,7-dimethoxyquinazolin-4-amine hydrochloride (L3), 5-(6,7-dimethoxyquinazolin-4-ylamino)quinolin-8-ol hydrochloride (L4), respectively, to afford [RuIICl2(DMSO)2(L1)] (1), [RuIIICl3(DMSO)(L1)] (2), [RuIIICl4(DMSO)(H-L2)] (3), [RuIIICl4(DMSO)(H-L3)] (4), and [RuIIICl3(DMSO)(H-L4)] (5), which were characterised by mass spectrometry, NMR, elementary analysis and single crystal X-ray diffraction (complex 1). Experimental screening (ELISA) showed that complexes 1, 2 and 3 are remarkably inhibitory towards epidermal growth factor receptor (EGFR) with IC50 values at submicromolar or nanomolar level. Docking studies indicated that complexation with ruthenium has little interference with the formation of the two essential H-bonds between the N3 of the quinazoline ring in L1 and L2 and O–H of Thr766 through a water molecule, and the N1 of the quinazoline ring and N–H of Met769 in EGFR. Moreover, complex 2 was shown to be more active against the EGF-stimulated proliferation of human breast cancer cell line MCF-7 than the better EGFR inhibitor 4-(3′-chloro-4′-fluoroanilino)-6,7-dimethoxyquinazoline, being more potential to induce early-stage apoptosis than gefitinib. These imply that apart from inhibiting EGFR, complex 2 may involve in regulating other biological events related to the proliferation of MCF-7, implicating a novel type of multi-targeting metal-based anticancer agents.A ruthenium complex (see picture) bearing an EGFR inhibiting 4-anilinoquinazoline ligand exhibits selectively anti-proliferative activity on EGF-stimulated growth of MCF-7, being more active to induce early-stage apoptosis than gefitinib.