A new series of 4,5-dihydro-1H-thiochromeno[4,3-d]pyrimidine derivatives have been designed and synthesized.The antitumor activities of the target compounds have been evaluated in vitro against two human cancer cell lines including A549 (human alveolar adenocarcinoma cell) and H460 (human lung cancer) by MTT assay.Most of the target compounds exhibited significant antitumor activities against A549 and H460 cancer cell lines.The most potent compound 4-(benzo[d][1,3]dioxol5-yl)-8,9-difluoro-2-(4-methylpiperazin-1-yl)-4,5-dihydro-1H-thiochromeno[4,3-d]pyrimidine (CH05) (IC50=0.44 M,3.07 M) was 2.0 and 8.4 times more active than gefitinib (IC50=0.89 M,16.81 M) against A549 and H460 cell lines,respectively. A new series of 4,5-dihydro-1H-thiochromeno [4,3-d] pyrimidine derivatives have been designed and synthesized. The antitumor activities of the target compounds have been evaluated in vitro against two human cancer cell lines including A549 alveolar adenocarcinoma cell) and H460 (human lung cancer) by MTT assay. Host of the target compounds exhibited significant antitumor activities against A549 and H460 cancer cell lines. The most potent compound 4- (benzo [d] [1,3] dioxol 5- yl) -8,9-difluoro-2- (4-methylpiperazin-1 -yl) -4,5-dihydro- 1H- thiochromeno [4,3-d] pyrimidine (CH05) (IC50 = 0.44 M, 3.07 M) was 2.0 and 8.4 times more active than gefitinib (IC50 = 0.89 M, 16.81 M) against A549 and H460 cell lines, respectively.