The invention discloses a novel synthesis process of entecavir monohydrate. In the method, monomer cyclopentadiene serves as a starting raw material, the entecavir hydrate is prepared by thirteen steps, i.e. salification, silanization, condensation, reduction, resolution, esterification, reduction, desilanization, hydroxyl protection, epoxidation, condensation, allylation, deprotection. According to the invention, raw material is available and is low in price, synthesis operation is simple, reaction conditions are mild and are easy to control, reaction selectivity is good, and yield is high, thus the process is applicable to industrial production.