We examined expression and function of osteopontin (OPN) in oral cancer cell lines using antisense oligonucleotide (AS). Quantitative real-time RT-PCR showed that expression in BSC-OF cells was significantly higher (10-fold) than that in KB cell. AS-study showed that foci of AS-treated BSC-OF cells possessed thin processes and radiated morphologically, although BSC-OF cells showed round foci. Cell growth in AS-group was lower (<80%) than the control. Invasion ability in AS-group became significantly lower (P<0.01). These results suggest that BSC-OF cell is useful for over-expression of OPN, and that OPN contributes to morphology, growth and invasion.