In this study we showed a pivotal role of PKM2 acting as a non-metabolic function to promote cancer cell progression in human oral squamous cell carcinoma (OSCC) through the induction of epithelial-mesenchymal transition (EMT), which is crucial for the potential in cancer cell invasion, and post-translational TGIF2 degradation. Here, TGIF2 is linked to oral cavity squamous cell carcinoma.