Ten novel 2-(2-substituted 1,3,4-thiadiazol-5-yl)benzisoselenazol-3(2H)-one derivatives (6) were synthesized by the condensation of 2-chloroselenobenzoyl chloride and 2-amino-5-substituted 1,3,4-thiadiazole according to substructure link principle, and structurally confirmed by IR, ¹H NMR, ESI-MS techniques and elemental analysis. The antiproliferative activities against three tumor cells were tested using CCK-8 method. The results indicated that 6h against A-549, 6a, 6b, 6d, 6e, 6f, 6g, 6h, 6j against MCF-7 and 6a, 6b, 6d, 6e, 6f, 6g against SSMC-7721 showed better activities than positive control Ebselen did, which suggested such compounds with a certain selectivity to the three tumor cells and were worth further investigation.