4-Methylumbelliferone (4-methyl-7-hydroxycoumarin, 1) is a coumarins natural product with important biological activity. Firstly, 4-methylumbelliferone (1) was synthesized from resorcinol and ethyl acetoacetate by Pechmann reaction. Nine coumarin derivatives (2~10) were then synthesized through Mannich reaction, acetylation, Fries rearrangement, O-methylation, Baeyer-Villiger oxidation, O-prenylation and Claisen rearrangement from 4-methylumbelliferone (1). Their inhibitory activities on human cervical carcinoma Hela cells were evaluated in vitro. The biological testing results showed that 4-methyl-5-prenyl-8-hydroxy-7-methoxycoumarin (10, IC50 = 28.58 μmol/L) displayed stronger activity than the positive control drug cis-Platin (IC50 = 41.25 μmol/L), which is worthy of further study.