In order to seek better ligand for anticancer drug, we choose 1,10-phenanthroline (phen) and 2,9-dimethyl-1,10-phenanthroline (2,9-dmp) as predominant ligands, and synthetize two complexes:[(DMF)Cu(phen)(NO 3 ) 2 ] (1) and [(DMF)Cu(2,9-dmp)(NO 3 ) 2 ] (2) (DMF is dimethyl formamide). As for the five kinds of cancer cells, including A-549, Bel-7402, HCT-8, MDCK and L-1210 cells, our complexes showed higher inhibition ratio compared with anticancer drug 5-Fu (fluorouracil), ligand phenanthroline and Cu(NO 3 ) 2 . It's worth noting that complex 2's anticancer activity is much more efficient than that of complex 1. This is because there are di-substituted-methyl in 2,9-dmp. By calculating, we found Δ complexes <Δ phenanthroline which showed that the energy gap between π ⁎ and π of the phenanthroline is decreased through coordination with Cu II . Computational ΔG 2 <ΔG, and bond length (CuN) 1 <(CuN) 2 revealed that the coordinated 2,9-dmp is easier to dissociate with Cu II than phen, which is confirmed by the absorption peak at 460nm in UV–visible (UV–vis) spectra of complex 2. In summary, the phenanthroline is activated by Cu II -coordination, which is beneficial for anticancer. More importantly, the substituted-methyl radicals stimulated the phenanthroline and enhanced the anticancer properties more efficiently.