Purpose: Wnt5a is the most important Wnt protein activating the non-canonical Wnt pathway. It regulates proliferation, differentiation, migration, adhesion and polarity of the cell. Clinical studies have shown that Wnt5a could act as a prognostic marker in various cancers. It seems that Wnt5a acts both as a tumor suppressor (breast, thyroid, colon and livercancer) and as a tumor promotor (malignant melanoma, pancreatic and gastric cancer). In oral squamous cell carcinoma (OSCC) a number of Wnt and Frizzled genes are expressed, mostly Wnt5a and Frizzled-5 but the role of Wnt5a has not yet been thoroughly elucidated. The aim of this study is to evaluate the role of Wnt5a in oral OSCC and its influence on the cell proliferation, migration and invasion. Material and methods: The protein content of Wnt5a in two OSCC cell lines (SCC25 and SCC9) was determined by Western blotting. The influence of rWnt5a and two Wnt5a-derived hexapeptides: Foxy5 (an agonist that mimics Wnt5a activity) and Box5 (an antagonist that inhibits Wnt5a) on the migration and proliferation in OSCC cell lines was studied by a scratch assay and BrdU. Invasion influenced by rWnt5a was studied using Boyden chambers. Results: Both cell lines express Wnt5a. Dose–response curves of rWnt5a in SCC9 and SCC25 indicate that Wnt5a increases migration with statistically significant effective concentration at 0.4 μg/ml but has no effect on the proliferation of the two cell lines. To confirm this we used Foxy5 and Box5. Foxy5 increases migration with statistically significant effective concentration at 150 μM while Box5 inhibits Wnt5a effect on the migration. Foxy5 and Box5 have no influence on proliferation. Invasion was increased by rWnt5a. Conclusions: The results demonstrate that Wnt5a increases migration and invasion but has no influence on proliferation in OSCC cell lines.