Oral squamous cell carcinomas (OSCCs), a major public health problem worldwide, are the most common neoplasms of the head and neck. The most important prognostic indicator for patients with OSCC is metastasis to cervical lymph nodes or distant organs. Galectin-9 is correlated with cellular adhesion and aggregation in melanoma cells. To investigate expression levels of galectin-9 mRNA and protein, we performed qRT-PCR and Western blot analyses on OSCC cell lines (Ca9-22, HSC-2, and HSC-3) and normal oral keratinocytes (NOKs). Galectin-9 mRNA and protein were commonly down-regulated in OSCC cell lines compared with NOKs. We further analyzed Ca9-22, which had the lowest expression of galectin-9. We then transfected the galectin-9 cDNA into Ca9-22 cells to examine whether overexpression of galectin-9 increases cellular adhesion in vitro. An adhesion assay using a fibronectin and collagen I coating plate revealed an increased cellular adherence ratio in overexpressed galectin-9 cells compared with nontransfected cells (p < 0.05). The data suggest that galectin-9 is correlated with oral cancer cell-matrix interactions and may therefore play an important role in the metastasis of OSCCs.