A series of tetracyclic diterpenoids bearing α-methylenelactone group were synthesized from stevioside. Some of them exhibited significant cytotoxicity against all the six tumor cell lines with the IC50 values ranging from 0.09 to 5.71μM. A series of tetracyclic diterpenoids bearing the α-methylenelactone group have been synthesized and screened for their in vitro anti-tumor activities against six human cancer cell lines. The results showed that compounds 1c, 2a and 2b exhibited significant cytotoxicity superior to the positive control doxorubicin hydrochloride against MDA-MB-231, K562 and HepG2 cell lines. In particular, compound 2b was identified as the most promising anticancer agent against HepG2 cells with IC50 value of 0.09μM.