The current research work deals with the design, synthesis of a series of 6-substituted- 4-hydroxy-1-(-4-substitutedphenyl)sulfonyl)quinolin-2(1H)-thiones [III A (1-3), III B (1-3), III C (1-3), III D (1-3) ]derivatives and evaluation of their in vitro anticancer activity. Molecular docking studies of the title compounds were carried out using Molegro Virtual Docker (MVD-2013, 6.0) software. The synthesized compounds exhibited well conserved hydrogen bonds with one or more amino acid residues in the active pocket of EGFRK tyrosine kinase domain (PDB ID: 1m17). The MolDock Score of compound (III D-3) was (-77.1739) which is comparable to that of the standard ligand(-121.469) and imatinib (-116.362). Thus, the synthesized derivatives possessed a potential to bind with some of the residues of the active site and can be further developed into potential pharmacological agents. The compounds were synthesized using appropriate synthetic route and all the synthesized compounds were characterized by IR, NMR spectral data. Twelve derivatives were tested for their in vitro anticancer activity using A549 cell line. Compound (III D-3) was found to be the most cytotoxic as compared to the other synthesized derivatives, with IC₅₀ values of 228.51 µg/ml against A549 cell line was more potent than standard drug Imatinib with IC₅₀ value of 370µg/ml.