A series of aminopyridazin-3(2H)-one derivatives has been designed and synthesized. Their antiproliferative activities were evaluated against three human cancer cell lines (SH-SY5Y human neuroblastoma, K562 human myelogenous leukemia and AGS gastric cancer cell lines) using the MTT assay. The preliminary activity test displayed that compound 8a exhibited comparable activities against all test cells with the positive control fluorouracil. Meanwhile compounds 8b, 8e and 9c-e displayed selective antiproliferative activities for SH-SY5Y cells. Furthermore, compounds 8a-b with low-micromole GI50 value for SH-SY5Y cells induced apoptosis with cell cycle arrest at G0/G1 phase in SH-SY5Y cells in a dose-dependent manner.