Abstract: Twenty-five N "-phenylmethylene-2-(3-pyridyl) quinoline-4-hydrazide derivatives (yield: 20.4- 42.6%) were designed and synthesized based on bioelectronic isosteric principle with STX-0119 as the lead compound，and the product structure was confirmed by 1H NMR，MS，13C NMR. The in vitro antitumor activity of the target compounds was evaluated using the MTT assay and the Trypan Blue assay. Human breast cancer cell line MCF-7 cells，human lung cancer cell line A549 cells，human chronic myelogenous leukemia cell line K562 cells，and human acute B-lymphoblastic leukemia cell line RS4:11 cells were used as test cell lines. Target compound Ⅶr exhibited the strongest cell proliferation inhibitory activity against A549 cells with IC50 = 7.42 ± 0.83 μmol/L，target compound Ⅶq showed the strongest cell proliferation activity against RS4:11 cells with IC50 = 2.4 ± 0.17 μmol/L，target compound Ⅶl not only exhibited the strongest proliferation activity against MCF-7 cells (IC50 = 4.91 ± 0.33 μmol/L) but also showed the strongest proliferation activity against K562 cells (IC50 = 1.24 ± 0.19 μmol/L)，molecular docking results indicate that its anti-tumor effect may be related to the STAT3 pathway，which deserves further in-depth research.