To detect whether Col-Ⅰ has some contribution to migration and proliferation of head and neck squamous carcinoma cell (HNSCC) in tumor microenvironment, transwells were applied to measure cell migration, cell velocity and cell scattering were analyzed by Zeiss Axiovert inverted microscope. The expression of E-cadherin as one of cell surface adhesion molecules and cell location of β-catenin were detected by Western blotting and/or immunofluorescence, then proliferation was analyzed by MTT and the PCNA expression. Results showed that Col-Ⅰ promoted cell metastasis, cell velocity and cell scattering, which E-cadherin was repressed possibly by the increased phosphorylation of β-catenin. The nuclear translocation of β-catenin led to an increasing expression of cyclin D1 and proliferation. Together, a conclusion is made that Col-Ⅰ promotes HNSCC metastasis via upregulation of phosphorylation of β-catenin and proliferation by the nuclear translocation of β-catenin.