Nine Schiff-Base substituted 3,5-bis(arylidene)-4-piperidone derivatives,3a-i,were prepared by Claisen-Schmidt condensation reaction,SnCl2/HCl reduction and Schiff-Base condensation reaction.The structures of nine compounds were characterized by FTIR,NMR and elemental analysis.Their antitumor activities against human neoplastic cell lines SGC-7901,A549,HCT116,HeLa,HePG2,K562,THP-1,U937,MCF-7 and their cytotoxicities toward LO2 were subsequently evaluated by MTT method.The results showed that some of them have good antitumor activities,and their IC50 values were lower than 1.0 μmol/L,while the cytotoxicities of 3a,d-f toward LO2 cells were markedly lower than that of DOX.The structure-activity relationships indicated that the antitumor activities of F-substituted 3a-c were better than those of Br- or Cl-substituted 3d-i.Molecular docking model,PCR and Western Blot showed that compounds 3b and 3i could exert obvious inhibition on the active site of Bcl-2 protein.