BACKGROUND: Head and neck squamous cell carcinomas are a group of heterogeneous diseases that occur in the mouth, pharynx and larynx and are characterized by poor prognosis. A low overall survival rate leads to a need to develop biomarkers for early head and neck squamous cell carcinomas detection, accurate prognosis and appropriate selection of therapy. Therefore, in this paper, we investigate the biological role of the pseudogene and associated genes and and their potential use as biomarkers. METHODS: Based on TCGA data and the UALCAN database, , and expression profiles and clinicopathological features with TP53 gene status as well as expression levels of correlated genes were analyzed in patients' tissue samples. The selected genes were classified according to their biological function using the PANTHER tool. Gene Set Enrichment Analysis software was used for functional enrichment analysis. All statistical analyses were performed using GraphPad Prism 5. RESULTS: In head and neck squamous cell carcinomas, significant up-regulation of the pseudogene, and genes' expression between normal and cancer samples were observed. Moreover, the expression of , and depends on the type of mutation in TP53 gene, and they correlate with genes from p53 pathway. expression was significantly correlated with as well as , as was expression with . Significant differences between expression levels of , and in head and neck squamous cell carcinomas patients were also observed in clinicopathological contexts. The contexts taken into consideration included: T-stage for ; grade for , and ; perineural invasion and lymph node neck dissection for and HPV p16 status for , and . A significantly longer disease-free survival for patients with low expressions of and , as compared to high expression groups, was also observed. Gene Set Enrichment Analysis indicated that the high-expressing group of patients have the most deregulated genes connected with DNA repair, oxidative phosphorylation and peroxisome pathways. For , altered genes are from DNA repair groups, Myc targets, E2F targets and oxidative phosphorylation pathways, while for , changes in E2F targets, G2M checkpoints and oxidative phosphorylation pathways are indicated. CONCLUSIONS: and can be used as a prognostic biomarker in head and neck squamous cell carcinomas diagnostics. Moreover, patients with high expressions of , or have worse outcomes due to upregulation of oncogenic pathways and more aggressive phenotypes.