Novel water-soluble prodrugs of combretastatin A-4 (5-8) were synthesized and evaluated for their in vitro cytotoxicity against lung carcinoma A549. Compound 5, bearing phosphoryl choline (PC) moiety, showed 90% inhibition at 32 μg/mL concentration after 24 h. The findings showed the PC derivative would be a promising candidate for the development of new water-soluble prodrug of cytotoxic combretastatin A-4.