In order to search for antitumor compounds, nine L-phenylalanine dipeptide derivatives containing phosphonate backbones were designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR and MS. These compounds were tested for their antitumor activities in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The results showed that some of the target compounds had inhibitory effect on the proliferation of the tumor cells and showed potential antitumor activity. Among them, espectively, compound Ⅲi showed remarkable activities against A-549 and EC-109 with IC50 values of 6.8 ± 0.9 μmol/L and 7.0 ± 1.2 μmol/L, respectively, which were close to cisplatin.