Objective:To design and synthesize novel norcantharidin derivatives and to investigate their anti-tumor activities in vitro.Methods: Novel norcantharidin analogues were synthesized through several steps using furan and maleic anhydride as the starting material.All the target compounds were confirmed by 1HNMR,ESI-MS and element analysis,and screened against 4T1(breast cancer cell).The compound 7a and 7c with better activity were further screened against LLC(lung cancer cell),SK-HEP-1(human hepatoma cell) and ABAE(vascular endothelial cell).Results: Totally 18 novel target compounds were obtained.The results of anti-cancer test showed that compounds 7a and 7c had anti-tumor activity and less damage to normal cells.Conclusion: Compounds 7a and 7c have inhibitory effect against 4T1 cells,LLC cells and SK-HEP-1 cells.Compound 7c shows less damage to ABAE(normal vascular endothelial cells) than norcantharidin and is worth further studying.