Cancer-related inflammation has emerged as one of the hallmarks of cancer. The effect of inflammation on most cancers is two-edged, with cancer also affecting the process of inflammation. Various factors plays a crucial role in tumor suppression such as TLR-2, Mast cells, tumor infiltrating lymphocytes (TILs) and tumor-associated macrophages. Viral-associated HNSCC has become a significant global burden. Rapid advances in the field of immuno-oncology and the constantly growing knowledge of the immunosuppressive mechanisms and effects of tumor cancer have allowed for the use of effective and personalized immunotherapy as a first-line therapeutic procedure or an essential component of a combination therapy for primary, relapsed and metastatic HNSCC. Immunological typing of tumour should be considered with decisive role in diagnostic and prognostic pathology in future.