Squamous cell carcinoma of oral tongue belongs to highly invasive malignancies of head and neck area. The natural isoquinoline alkaloid berberine has demonstrated anti-tumor potential in various cancer types. This research was aimed to study in vitro effects of berberine in squamous cell carcinoma of oral tongue. Berberine reduced the proliferation of CAL-27 cells in a dosedependent manner (IC50 = 36μM). Furthermore, berberine strongly inhibited invasion of squamous cell carcinoma of oral tongue cells (EC50 = 0,9μM). Anti-proliferative and anti-invasive actions displayed by berberine in CAL-27 cell line suggest the in vitro anticancer efficacy of the natural isoquinoline alkaloid.