Carcinogenesis is often associated with alteration of epigenetic marks, including histone modifications. The global level and local distribution of specific histone modifications have been revealed to be prognostic factors in many cancers. However, the functional roles of histone modifications in oral squamous cell carcinoma (OSCC) remain unclear. This study investigates the levels of various histone modifications in 6 types of OSCC cell lines. We found that the level of H3K9me3 was significantly high in metastatic cell lines. In addition, the loss of H3K9me3 by SUV39H1 and SUV39H2 knockdown suppressed cell proliferation and cell migration. Our results indicate that a high level of H3K9me3 could be a marker of metastasis and possibly a therapeutic target for OSCC treatment.