Syndecan-1 has been shown to be a prognostic factor in various types of tumors, suggesting its correlation with malignancy and metastasis. In the present study, we examined the expression of syndecan-1 in oral cancer cell lines and tested whether transfection of an siRNA against human syndecan-1 affected the malignant potential of these cells. Seven different human oral cancer cell lines (HSC2, HSC3, HSC4, Ca9-22, SAS, KB and BSC-OF) were used. To evaluate the mRNA expression of syndecan-1 in these cell lines, quantitative real-time RT-PCR (QRT-PCR) was carried out. In order to examine syndecan-1 function, siRNA was transfected into the cells, after which the cell growth rate and invasive ability were evaluated. As a negative control, a random sequence siRNA was used. QRT-PCR showed that syndecan-1 was expressed in Ca9-22 cells and that it was significantly higher (> 10-fold) than in the other oral cancer cell lines. Transfection of syndecan-1 siRNA was carried out on Ca9-22 cells, which increased their growth rate 1.4-fold above controls. The invasive ability of Ca9-22 cells treated with syndecan-1 siRNA was significantly higher (2-fold; n=5) than the controls. These results suggest that Ca9-22 oral cancer cells are a useful model to study syndecan-1 function and they show that syndecan-1 directly contributes to the growth and invasive ability of these cells.