Background:Cucurbitacin IIb (CIIb) from Ibervillea sonorae has great capacity to suppress the proliferation of cancer cells and induce apoptosis. In this study, the molecular mechanisms related to the antiproliferative and apoptosis induction capacity of CIIb (derivate from Ibervillea sonorae) in HeLa cells was investigated. Materials and Methods: By trypan blue exclusion assay the viability and the cell proliferation effect of CIIb was evaluated. The effect of CIIb on the mitochondrial membrane potential was develop by flow cytometry using JC-1. The activity of the caspase-3 and caspase-9 was evaluated through of flow cytometry using commercial kits. By (Fluorescence-Activated Cell Sorting) FACS analysis the effect of CIIb on the cell cycle was investigated. Western blot was used to evaluated the inhibitory effect of CIIb on STAT3 signaling pathway and cyclin –B1as well as DNA damage by comet assay. Results: The study of the mechanism of action revealed that CIIb was able to disrupt the mitochondrial membrane potential (ΔΨm) and consequently activate the caspases -3 and -9, how a result of the activation of the intrinsic pathway of the apoptosis. Likewise, CIIb induced cell cycle arrested in S and G2/M after 24h of treatment. CIIb also reduced the expression of STAT3 and cyclin –B1 and finally CIIb induces a great antiproliferative effect at 48 and 72h inducing DNA damage. Conclusion: These results demonstrated that CIIb induce apoptosis and cell cycle arrested in HeLa via inhibition of STAT3.