This study was performed to investigate mistletoe extract-induced apoptosis in oral squamous cell carcinoma. In vivo study, HN22 cells were xenografted in nude mice. After tumor was experimentally induced, mistletoe extract was directly injected on the tumor mass. The specimens were evaluated using light and transmission electron microscopes. In vitro study, HN22 cells were cultured and exposed to mistletoe extract. The cells were evaluated using transmissin electron microscope. To evaluate apoptotic cells, flow cytometric analysis was done. The results were obtained as follows: 1. Light microscopic view of tumor mass showed necrosis at 2-4 weeks. 2. Transmission electron micrographs of tumor mass showed apoptosis and necrosis. 3. In TEM view of cell lines, necrosis and apoptosis were shown with mistletoe extract at $300{mu}g/ml$, apoptosis was shown with mistletoe extract at $100{mu}g/ml$. 4. In flow cytometric analysis, early and late apoptosis was shown when using caspase-3Ab and annexin-V, but no significant change was noted when using mebstain and Apo2.7 Ab. In this study, mistletoe extract induced necrosis and apoptosis in the tumor mass was induced by HN22 cells, early and late apoptosis in vitro study. Mistletoe extract was likely to induce cell death in oral squamous cell carcinoma through apoptosis.