A series of 1H-thieno[2,3-c] chromen-4(2H)-one derivatives were synthesised through Knoevenagel condensation of substituted flavanones with thiazolidine-2,4-dione in ethanol in the presence of piperidine. The mechanism of the reaction was proposed. All synthesised compounds were characterised by IR, H-1 NMR, C-13 NMR, HRMS, and elemental analysis. The structure of 2-(3-chlorophenyl)1H- thieno[2,3-c] chromen-4(2H)-one was confirmed by a single crystal X-ray diffraction analysis. A preliminary antitumour screening showed that 2-(2-fluorophenyl)-1H-thieno [2,3-c] chromen-4(2H)-one had moderate to good activity against A549, BGC-823, HCT116 and MDA-MB-453 cancer cell lines, and 2-(3,4-dimethoxyphenyl)-1H-thieno[2,3-c] chromen-4(2H)-one displayed similar activity against these four kinds of cancer cells compared with the reference drug.