An efficient, one-pot multicomponent reaction of novel pyrazolo-oxothiazolidine derivatives was achieved by condensation of 1-(benzofuran-2-yl)-3-(substituted-arylprop-2-en-1-ones, thiosemicarbazide and dialkyl acetylenedicarboxylates under the optimized reaction conditions. Synthesised compounds were evaluated for their antiproliferative activity against A549 human lung cancer cell line. Among all the tested compounds, 4a (IC50 - 0.930 μg/mL), 4e (IC50 - 1.207 μg/mL), 4f (IC50 - 0.808 μg/mL), 4g (IC50 - 1.078 μg/mL), 4h (IC50 - 0.967 μg/mL) and 4j (IC50 - 2.445 μg/mL) showed promising activity compared with standard drug Sorafenib (IC50 - 3.779 μg/mL). Molecular docking studies indicated that compound 4f had the greatest affinity for catalytic site of receptors EGFR (PDB ID code: 1 M17) and VEGFR2 (PDB ID code: 4AGD, 4ASD). These novel pyrazolo-oxothiazolidine derivatives can be promising therapeutic agents for A549 human lung cancer cell line.