New 5-subistituted-4-thiazolidinone derivatives 4a-g were synthesized through chloroacetylation of 2-ami no- benzothiazole derivatives and further cyclyised by the use of ammonium thiocyanate then subjected to d ifferent aryl and heteroaryl aldehydes. All the prepared compound s were evaluated for their antitumor activity again st human breast (MCF-7) and non-small cell lung (A549) cance r cell lines. Most of compounds showed moderate ant itumor activity especially the 5-(2-thiophen-arylidene)-4- thiazolidinone derivative 4a with IC 50 13.25 μ M against human breast MCF-7 cell line and 12.08 μM against non-sma ll cell lung A549 cell line. Also, 5-(2-methoxy-ary lidene)-4- thiazolidinone derivative 4b have the antitumor activity with IC 50 14.51 μ M against MCF-7 cell line and 13.25 μM against A549 cell line. All the prepared compounds were docked against EGFR using 4-anilinoquinazoline inhibitor (4AQ) (PDB ID: IM17) in away to explore their bindi ng mode.