During hypoxia, cells undergo transcriptional changes to adjust to metabolic stress, to promote cell survival, and to induce pro-angiogenic factors. Hypoxia-induced factors (HIFs) regulate these transcriptional alterations. Failure to restore oxygen levels results in cell death by necrosis. IL-1alpha is one of the most important mediators of sterile inflammation following hypoxia-mediated necrosis. During hypoxia, IL-1alpha is up-regulated and released from necrotic cells, promoting the initiation of sterile inflammation. This study examined the role of IL-1alpha transcription in initiation of hypoxic stress and the correlation between IL-1alpha transcription and HIFalpha factors. In an epithelial cell line cultured under hypoxic conditions, IL-1alpha transcription was up-regulated in a process mediated and promoted by HIFalpha factors. IL-1alpha transcription was also up-regulated in hypoxia in a fibroblast cell line, however, in these cells, HIFalpha factors inhibited the elevation of transcription. These data suggest that HIFalpha factors play a significant role in initiating sterile inflammation by controlling IL-1alpha transcription during hypoxia in a differential manner, depending on the cell type.