This study is to investigate the antitumor activity of CIP-36 on multidrug resistant human oral squamous carcinoma cell line (KBV200 cells) in vitro and the possible anticancer mechanisms.  MTT assay, Hoechst fluorescein stain, RT-PCR and immunohistochemistry were carried out on KBV200 and KB cells.  The growth of many tumor cells was obviously inhibited by CIP-36, especially the multidrug resistant cells KBV200.  Obvious apoptosis could be observed in the Hoechst 33342 staining experiments.  The results of RT-PCR showed that the levels of p53, p21, caspase-3 and bax mRNA increased, and meanwhile the expression of mdr-1 and bcl-2 mRNA decreased in a dose-dependent manner.  The data were significantly different from that of vehicle.  The expression of P-gp significantly decreased with the increasing dosage of CIP-36 examined by immunohistochemistry.  It can be concluded that CIP-36 could change resistance-related genes and proteins to overcome multidrug resistance in the KBV200 cell line.