The canonical Wnt pathway is related to regulation of embryogenesis, cell differentiation and proliferation. Various proteins are necessary for proper signal transduction and β-catenin serves as the main mediator. In off-state of the Wnt pathway β-catenin undergoes proteasomal degradation, while in on-state increase of cytoplasmic concentration of β-catenin occurs followed by β-catenin translocation into the cell nucleus. Interaction between β-catenin and TCF/LEF transcription factors activates the expression of over hundred target genes of the Wnt pathway. Highly active Wnt signaling is observed in many cancers, including head and neck squamous cell carcinomas. Knowledge of the functional structure of the canonical Wnt pathway enables search of therapeutic molecular targets to effectively inhibit transcriptional activity of β-catenin in cancer cells.