Tetrahydroisoquinoline and its derivatives have a wide range of biological activities, such as antitumor, antimicrobial, and analgesic properties and so on. Some tetrahydroisoquinoline alkaloid derivatives have been studied as antitumor drug molecules, but 2-benzyl-7-substituted-ethoxy]-3, 4-dihydro-1(2H)-isoquinolinone series have not been reported yet. In this paper, we would like to report the design, synthesis, and biological evaluation of the novel tetrahydroisoquinoline derivatives. Among those compounds, four new tetrahydroisoquinoline derivatives have not been reported before. All the newly synthesized compounds were characterized by 1H NMR and their antitumor activities were evaluated by using HT-29, K562 and HepG2 cell line. 2-Benzyl-7-[2-(tert-butyl-4-piperazinecarboxylate) ethoxy]-3, 4-dihydro-1(2H)-isoquinolinone demonstrated good antitumor activity against K562 cancer cell with an IC50 of 1.58 lM. © Springer-Verlag Berlin Heidelberg 2014.