A novel series of phthalazine derivatives bearing isoindol-1,3-dione moiety were synthesized by treating 2-[4-(4chlorophthalazine-1-yl)phenyl]-1H-isoindole-1,3-(2H)-dione 3 with various chemical reagents.The newly synthesi- zed compounds were characterized on the basis of their spectral (1H NMR, 13C NMR, Ms, IR) analyses. In vitro, most of the synthesized derivatives were screened for their antitumor activity against HepG2 cells using MTT assay. Compounds 11, 18 and 19c showed the most potent cytotoxic effect concluded from their IC50 values 217.4, 240.3 and 234.5 µg/ml respectively.