As a main bioactive component extracted from Evodiae fructus, evodiamine has a variety of pharmacological activities. In this paper, evodiamine was chosen as starting material to react with different halides. Upon treatment of TFA, a series of novel ring-opening evodiamine derivatives 3a-o were successfully synthesized in a moderate to high yields. These obtained compounds exhibit a moderate to good anti-tumor activity against BGC803 and SW480 in vitro test by MTT assay. The results showed that hexyl substituted evodiamine derivative (3j, R = hexyl) has a strong antitumour activity against BGC803 and SW480.