We have performed a 3D-QSAR/CoMFA analysis of the cytotoxic activities of thirty-five 3-arylisoquinoline derivatives against SK-OV-3 tumor cell line. The results suggested that the electrostatic, steric and hydrophobic factors of 3-arylisoquinolines were strongly correlated with the antitumor activity. Considerable predictive ability (cross-validated r2 as high as 0.841) was obtained through CoMFA.