Influence of an intracranial aneurysm (IA) rupture on the expression of miRNAs and the potential significance of the resulting changes remains poorly understood. We aimed to characterize the response to the IA rupture through the analysis of miRNAs in peripheral blood cells. Expression of small RNAs was investigated using deep transcriptome sequencing in patients in the acute phase of an IA rupture (first 72 h), in the chronic phase (3-15 months), and controls. A functional analysis and the potential interactions between miRNAs and target genes were investigated. We also measured the levels of proteins that were influenced by regulated miRNAs. We found that 106 mature miRNAs and 90 miRNA precursors were differentially expressed among the groups. The regulated miRNAs were involved in a variety of pathways, and the top pathway involved cytokine-cytokine receptor interactions. The identified miRNAs targeted the inflammatory factors HMGB1 and FASLG. Changes in their expression were detected at the mRNA and protein levels. IA rupture strongly influences the transcription profiles in peripheral blood cells. The regulated miRNAs were involved in the control of immune cell homeostasis. In summary, these results may aid in the elucidation of the molecular mechanisms that orchestrate the inflammatory response to IA rupture.