Despite the advances that lived science and medicine in recent decades, the prevalence and above all, the survival of patients with oral and, head and neck cancer, has not improved. Patients are diagnosed in advanced stages, where radiotherapy / surgery / chemotherapy are the only alternatives and do not provide acceptable results in most cases. For this reason, we believe that research at the basic level is the key to know more deeply the pathogenesis of these tumors. The cell cycle regulation is the basic mechanism of self-monitoring of healthy cells, which is fully deregulated in cancer, which causes an excessive and uncontrolled growth of tumor cells. In this special issue, we will try to elucidate the role of p16 and p21 in cell cycle control in oral squamous cell carcinoma, with the aim of translationally, apply the results to clinical practice.