A new series of 5-trifluoromethylpyrimidine derivatives were designed and synthesised as EGFR inhibitors. Three tumour cells A549, MCF-7, PC-3 and EGFR kinase were employed to evaluate their biological activities. The results were shown that most of the target compounds existed excellent antitumor activities. In particular, the IC50 values of compound 9u (E)-3-((2-((4-(3-(3-fluorophenyl)acrylamido)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)-N-methylthiophene-2-carboxamide against A549, MCF-7, PC-3 cells and EGFR kinase reached to 0.35 μM, 3.24 μM, 5.12 μM, and 0.091 μM, respectively. Additionally, further researches...