Hydrogen sulfide (H<sub>2</sub>S) is an endogenously produced signaling molecule that can be cytoprotective, especially in conditions of ischemia/reperfusion injury. However, H<sub>2</sub>S is also toxic, and unregulated accumulation or exposure to environmental H<sub>2</sub>S can be lethal. In <i>C. elegans</i> the hypoxia inducible factor (<i>
hif-1</i>) coordinates the initial transcriptional response to H<sub>2</sub>S and is essential to survive exposure to low concentrations of H<sub>2</sub>S. We performed a forward genetic screen to identify mutations that suppress the lethality of <i>
hif-1</i> mutant animals in H<sub>2</sub>S. The mutations we recovered are specific for H<sub>2</sub>S, as they do not suppress embryonic lethality or reproductive arrest of <i>
hif-1</i> mutant animals in hypoxia, nor can they prevent the death of <i>
hif-1</i> mutant animals exposed to hydrogen cyanide. The majority of <i>
hif-1</i> suppressor mutations we recovered activate the <i>
skn-1</i>/Nrf2 transcription factor. Activation of SKN-1 by <i>
hif-1</i> suppressor mutations increased the expression of a subset of H<sub>2</sub>S-responsive genes, consistent with previous findings that <i>
skn-1</i> plays a role in the transcriptional response to H<sub>2</sub>S. Using transgenic rescue, we show that overexpression of a single gene, <i>
rhy-1</i>, is sufficient to protect <i>
hif-1</i> mutant animals in H<sub>2</sub>S. The <i>
rhy-1</i> gene encodes a predicated O-acyltransferase enzyme that has previously been shown to negatively regulate HIF-1 activity. Our data indicate that RHY-1 has novel, <i>
hif-1</i> independent, function that promotes survival in H<sub>2</sub>S.