Objective：To investigate the effects of parthenolide（PTL） on the proliferation and apoptpsis of human proliferation and apoptosis of human small cell lung cancer cell line NCI-H446 and its mechanisms. Methods：Cell line provided by the cell library of Wuhan University. PTL was bought in company of gene operation. NCI-H446 cells were divided into control group and treatment group（1.5 μg/mL，2.0 μg/mL，2.5 μg/mL，3.0 μg/mL）. Treatment group were treated with different concentrations of PTL by adding corresponding concentration of PTL into culture medium，while control group was added equal volume culture medium without fetal calf serum. The cellular proliferative activity was determined by MTT assay. Morphologic changes were observed by fluorescence mi－croscope. The apoptosis rates of cell were examined by flow cytometry. The expression of NF-κB，Caspase-3，Caspase-8 and Caspase-9 genes of NCI-H446 cells was detected by RT-PCR assay. The expression of NF-κB，Caspase-3，Caspase-8 and Caspase-9 proteins of NCI-H446 cells was evaluated by Western blot. Results：Parthenolide inhibited the proliferation of NCI-H446 cells in a dose-de－pendent manner. Fluorescent microscopy showed that the number of NCI-H446 cells was reduced under Hoechst 33258 staining；the nucleus pycnosis fracture and apoptotic bodies were observed. Flow cytometry showed that the cell apoptosis rate was positively cor－related with the concentration of PTL，with statistically significant differences（P<0.05）. Compared with those of control group，RT-PCR and Western blot revealed that the expressions of mRNA and protein of NF-κB in NCI-H446 cells were reduced，at the same time，the expressions of Caspase-3，-8，-9 mRNA and proteins were increased with statistically significant differences（P<0.05）. Conclusion：PTL could repress cellular proliferation activity and induce apoptosis of NCI-H446 cells. The mechanisms could relate to inhibition of NF-κB signaling pathway and acti－vation of caspases system.