The adaptive response to hypoxia is accompanied by widespread transcriptional changes that allow for prolonged survival in low oxygen. Many of these changes are directly regulated by the conserved hypoxia-inducible factor-1 (HIF-1) complex; however, even in its absence, many oxygen-sensitive transcripts in Caenorhabditis elegans are appropriately regulated in hypoxia. To identify mediators of these non-HIF-dependent responses, I established a hif-1 mutant reporter line that expresses GFP in hypoxia or when worms are treated with the hypoxia mimetic cobalt chloride (cobalt chloride). The reporter is selective and HIF-independent, in that it remains insensitive to a number of cellular stresses, but is unaffected by mutation of the prolyl hydroxylase egl-9, suggesting that the regulators of this response pathway are different from those controlling the HIF pathway. I used the HIF-independent reporter to screen a transcription factor RNAi library and identified genes that are required for hypoxia sensitive and cobalt chloride-induced GFP expression. Three mediators of the HIF-independent response zinc finger protein BLMP-1, chromatin remodeling factor LIN-40, and T-box transcription factor TBX-38 were isolated as mediators of the HIF-independent response. First, we show that mutation of blmp-1 renders animals sensitive to hypoxic exposure and that blmp-1 it is required for appropriate hypoxic-induced expression of HIF-independent transcripts. Further, we demonstrate that BLMP-1 is necessary for an increase of hypoxia-dependent histone acetylation within the promoter of a non-HIF-dependent hypoxia response gene. Additionally, we explore BLMP-1’s role in two hypoxia-regulated physiological processes namely unfolded protein response and collagen formation. We also briefly investigate the role of LIN-40 in the hypoxia response.