Copper (II), palladium(II) and zinc(II) complexes of phosphonate derivative (S)-2-((phenoxyphosphono)(2-hydroxyphenyl) methyl-amino)-4-carbamoylbutanoic acid (PHCB) have been prepared and fully characterized by IR, elemental analysis, UV/Vis, 1 H-NMR, thermal analysis and Transmission Electron Microscope (TEM). The IR spectral data showed that the metal is coordinated to PHCB through carboxylic and NH groups. Carboxylic group behaves as a bidentate ligand with displacement of the proton, at the same time the metal coordinate with nitrogen atom of NH with the proton displacement. The complexes structure was supported by 1 H-NMR which shows the disappearance of both carboxylic and NH protons. The metal complexes stability was studied by thermal analysis. The activity of the organic ligands and their metal complexes as anticancer agents towards Hepatocellular carcinoma have been investigated. Zinc complex Zn(II)PHCB showed the highest activity with IC 50 = 9.58 µg/ml suggesting a promising anticancer drug in the future.