Abstract: To discover the novel compounds with biological activity, N-hetercycle substituted derivatives were synthesized based on the structure of benzofuran. A series of novel N-hetercycle substituted benzofuran derivatives( 2a - 2j )were synthesized by the reaction of 2-(4′-florobenzoyl)benzofuran with N-heterocyclic compounds. And the structures were characterized by ¹H NMR, ¹³C NMR and HRMS. Their anti-tumor activities were studied in vitro against a panel of human tumor cell lines(HeLa, A549 and H1975)by the MTT assay. The results indicate that compounds 2a , 2f and 2j are the most potent within this series of compounds against human tumor cell lines, showing that they are promising lead compounds for further structural modifications and biological evaluation.