The aim of this study was to explore whether mitochondrial- and histone stress cause any common changes in global gene expression. For this experiment, we performed RNA sequencing from control RNAi, cco-1 RNAi (mitochondrial stress) and his-3 RNAi (histone stress) treated C. elegans. Nematodes were collected at L4 larval stage, and total RNA was extracted with TriPure Isolation Reagent (Roche). An Illumina Truseq stranded mRNA library was prepared for nine samples (three biological replicates for each sample). Single-end sequencing with 100 cycles was performed by running the nine samples on one lane of an Illumina Hiseq 2500, yielding a minimum of 26 million reads per sample. Although the two stressors were found to have divergent effects on global gene expression, some biological processes such as innate immunity, heat shock response and chromatin remodeler expression are commonly upregulated upon both mitochondrial- and histone stress.