Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, and it early metastasizes into regional lymph nodes. We evaluated immunohistochemically the expression of the hypoxia marker hypoxia-inducible factor 1α (HIF-1α) as well as extracellular matrix protein tenascin C as a marker of stroma remodelling in a cohort of 160 PTCs. Expression of HIF-1α was seen focally accentuated in 100 of the 160 tumours (62.5 %) including 16 cases with equivocal staining (faint staining or only single-cell staining) and 84 cases with unequivocal staining. HIF-1α expression correlated with the degree of desmoplastic stromal reaction as well as with the expression of tenascin C (p < 0.001, Kruskal–Wallis test, respectively). Moreover, expression of HIF-1α was significantly associated with the presence of lymph node metastases (p < 0.001, Mann–Whitney test) as well as signs of invasion, namely, peritumoural and extrathyroidal invasion as well as angioinvasion (p = 0.024, p < 0.001, p = 0.017, Mann–Whitney test, respectively). Additionally, PTC with unequivocal HIF-1α nuclear staining was a larger tumour than PTC with negative (−) or equivocal HIF-1α expression (p < 0.001, Kruskal–Wallis test). Interestingly, the expression of HIF-1α was not significantly associated with BRAF V600E status (p > 0.05, Mann–Whitney test). Our data show that the expression of HIF-1α is associated with stroma remodelling processes within the tumour and, thus, may play an important role in an invasive behaviour of these tumours independent of BRAF mutation status.