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Oral squamous cell carcinoma (OSCC) is a major global health concern even with the developments in conventional therapies of cancer. This editorial aims to review the current genetic and molecular data of OSCC treatment with an emphasis on the Programmed cell death protein 1 (PD-1)/ligand PD-L1 pathway and novel biomarkers. Research shows that PD-1/PD-L1 inhibitors have the possibility to be used in OSCC treatment, and they mainly focus on improving immune functions. In this regard, salivary biomarkers provide early detection approaches with high sensitivity, especially chemerin and matrix metalloproteinase (MMP-9). Immune cell dynamics and personalized immunotherapy are important to be understood to achieve better therapeutic results. Some of them are tumor relapse, and the requirement of accurate prognostic indicators and diagnostic tests. Personalized medicine is one of the possibilities of using genetic knowledge in therapy. Some of the important areas for future research include improving the methods of early diagnosis, as well as identifying the possibilities of applying the concept of personalized medicine. Multicentre and cooperative work are essential for further improvement of the treatment of OSCC. Genetic and molecular studies provide a hope for better OSCC treatments and thus better patient outcomes worldwide.