OBJECTIVE To investigate the effects of Zhiling Capsule (ZLC) on the proliferation inhibition and apoptosis induction in human small cell lung cancer cell line NCI-H446. METHODS According to the different components of ZLC, NCI-H446 cells were treated with traditional Chinese medicine, Western medicine and ZLC compound groups. The rates of cell viability and colony formation were observed by MTT assay and colony formation assay respectively. Cell cycle assay, Bcl-2 protein expression, chondrial transmembrane potential and Caspase-3 activity were detected by flow cytometer. Apoptotic cells were detected by DNA fragmentation assay, Annexin-V FITC staining and TUNEL labeling methods. RESULTS After NCI-H446 cells were treated with various concentrations of drug groups, cell growth was significantly inhibited in a dose dependent manner. Cell colony formation was obviously lowered in the same way. The levels of chondrial transmembrane potential and Bcl-2 protein expression were decreased, while the levels of Caspase-3 activity were increased after the treatment. Typical DNA ladder were seen from gel electrophoresis, and apparent apoptotic peaks were observed by flow cytometer. Apoptosis occured in the early and late stage was identified by Annexin-V FITC staining and TUNEL labeling methods respectively. The ZLC compound group has stronger apoptosis induction than the other groups. CONCLUSIONS ZLC could efficiently inhibit growth and induce apoptosis in NCI-H446 cells, which may be related with the down-regulation of chondrial transmembrane potential and Bcl-2 protein expression and the up-regulation of Caspase-3 activity.