Objective: Acute organophosphorus(OP) pesticide poisoning is associated with dysfunctions in multiple organs, especially skeletal muscles, the nervous system and the heart. However, little is known about the specific microRNA (miRNA) changes that control the pathophysiological processes of acute OP poisoning damage. We aimed to explore miRNA expression profiles and gain insight into molecular mechanisms of OP toxic effects. Methods: MicroRNA expression was analyzed by TaqMan Human MicroRNA Array analysis and subsequent validated with quantitive PCR. The targets of the significantly different miRNAs were predicted with miRNA prediction databases, and pathway analysis of the predicted target genes was performed using bioinformatics resources. Results: 37 miRNAs were significantly different in the sera of poisoned patients compared to the healthy controls, including 29 miRNAs that were up-regulated and 8 miRNAs that were down-regulated. Functional analysis indicated that many pathways potentially regulated by these miRNAs are involved in skeletal muscle, nervous system and heart disorders. Conclusion: This study mapped changes in the serum miRNA expression profiles of poisoning patients and predicted functional links between miRNAs and their target genes in the regulation of acute OP poisoning. Our findings are an important resource for further understanding the role of these miRNAs in the regulation of OP-induced injury.