Vinylogous aldol condensation on some dihydropirimidine (DHPM) derivatives has been successfully performed using p-toluenesulfonic acid as a Brønsted acid catalyst. The pure products could be obtained without further purification. Employing this method, 20 styryldihydropyrimidine derivatives have been successfully synthesized wherein 19 of them are new compounds. The structures of the reaction products were elucidated by spectroscopic methods (IR, NMR, MS), while their cytotoxic activities were determined toward two cancer cell lines HeLa and MCF-7. Some compounds showed high activity better than doxorubicin as a positive control.