(1) Background: In head and neck squamous cell carcinoma, tumor hypoxia has been associated with radio/chemoresistance and poor prognosis, whereas human papillomavirus (HPV)-positive status has a positive impact on treatment response and survival outcomes. The aim of this study was to evaluate the expression and the potential prognostic value of hypoxia-induced endogenous markers in patients treated for squamous cell carcinoma of the nasal cavity and paranasal sinuses (SNSCC), and their correlation with HPV status. (2) Methods: In this monocentric study, patients treated in a curative intent for a SNSCC were screened retrospectively. Protein expression of CA-IX, GLUT-1, VEGF, VEGF-R1, and HIF-1α was determined by immunohistochemical staining, scored, and then correlated with overall survival (OS) and locoregional recurrence free survival (LRRFS). HPV status was assessed and correlated with hypoxic markers. (3) Results: 40 patients were included. A strong expression of CA-IX, GLUT-1, VEGF, and VEGF-R1 was detected in 30%, 32.5%, 50%, and 37.5% of cases, respectively. HIF-1α was detected in 27.5% of cases. High CA-IX expression was associated in univariate analysis with poor OS (p= 0.035), but there was no significant association between GLUT-1, VEGF, VEGF-R1, and HIF-1α expression, and OS/LRRFS. There was no correlation found between HPV status and hypoxia-induced endogenous markers (allp> 0.05). (4) Conclusions: This study provides data on the expression of hypoxia-induced endogenous markers in patients treated for SNSCC and underlines the potential role of CA-IX as a prognostic biomarker for SNSCC.