Estimating the post mortem interval (PMI) is still a crucial step in Forensic Pathology. Although several methods are available for assessing the PMI, a precise estimation is still quite unreliable and can be inaccurate. The present study aimed to investigate the immunohistochemical distribution and mRNA expression of hypoxia inducible factor (HIF‐1α) in post mortem gingival tissues to establish a correlation between the presence of HIF‐1α and the time since death, with the final goal of achieving a more accurate PMI estimation. Samples of gingival tissues were obtained from 10 cadavers at different PMIs (1–3 days, 4–5 days and 8–9 days), and were processed for immunohistochemistry and quantitative reverse transcription‐polymerase chain reaction. The results showed a time‐dependent correlation of HIF‐1α protein and its mRNA with different times since death, which suggests that HIF‐1α is a potential marker for PMI estimation. The results showed a high HIF‐1α protein signal that was mainly localized in the stratum basale of the oral mucosa in samples collected at a short PMI (1–3 days). It gradually decreased in samples collected at a medium PMI (4–5 days), but it was not detected in samples collected at a long PMI (8–9 days). These results are in agreement with the mRNA data. These data indicate an interesting potential utility of Forensic Anatomy‐based techniques, such as immunohistochemistry, as important complementary tools to be used in forensic investigations.