PD-L1 expression is critical in helping tumor cells evade the immune system. However, the level of PD‑L1 expression in non‑oropharyngeal head and neck squamous cell carcinoma (non‑OPHNSCC) and its association with patient prognosis remains unclear. A retrospective clinicopathological analysis was performed on 106 patients with non‑OPHNSCC diagnosed between 2007 and 2014. In the current study, tissue arrays from paraffin‑embedded non‑OPHNSCC samples obtained from patients were constructed, and PD‑L1 and p16INK4A expression were determined using immunohistochemistry. Systemic inflammatory factors, including C‑reactive protein, serum white blood cell, neutrophil, monocyte and lymphocyte counts were also analyzed. The current study demonstrated that PD‑L1 was overexpressed in 32.1%(34/106) and p16INK4A in 20.8%(22/106) of patients. The expression of PD‑L1 was associated with p16INK4A expression (P< 0.01) but was not associated with levels of systemic inflammatory factors. Tumor stage was determined to be a significant prognostic value (stage I/II vs. III/IV, P= 0.03), however, PD‑L1, p16INK4A or other clinicopathological factors were not. The current study identified an association between PD‑L1 and p16INK4A expression in non‑OPHNSCC. This may facilitate the development of anti‑PD1/PDL1 therapies to treat patients with head and neck cancer.