BACKGROUND AND AIM[|]Arsenic exposure continues to pose serious health threats globally. Epigenetic dysregulation plays an important role in arsenic toxicity, but the profile of plasma miRNAs in association with urinary arsenic remains largely unclear. We aimed to identify plasma miRNAs differentially expressed between high and low urinary arsenic groups, and further validate the identified miRNAs in a cohort population in China.[¤]METHOD[|]The discovery group, Shimen panel, consists of 19 high vs. low arsenic-exposed pairs selected from 1095 residents in an arsenic-contaminated area. The validation group, Wuhan-Zhuhai panel, consists of 53 participants in local communities with no known arsenic exposure. Plasma miRNAs were measured by microarray in the Shimen panel and by sequencing in the Wuhan-Zhuhai panel. Arsenic was measured by inductively coupled plasma mass spectrometry. We used paired Wilcoxon signed-rank test to identify miRNAs differentially expressed in the Shimen panel. We used linear regression model to obtain the beta coefficients of the association between urinary arsenic and miRNAs for the Wuhan and the Zhuhai participants separately, and pooled them together using fixed-effect meta-analysis. We performed KEGG pathway enrichment analysis for the identified miRNAs.[¤]RESULTS[|]In the discovery stage, we identified 16 miRNAs differentially expressed between high and low urinary arsenic groups in the Shimen panel (fold change > 2, P < 0.05). Of these, we validated seven miRNAs (miR-101-3p, miR-142-3p, miR-148a-3p, miR-15a-5p, miR-199a-3p, miR-27b-3p and miR-340-5p) to be positively associated with log-transformed urinary arsenic levels in the Wuhan-Zhuhai panel [pooled false discovery rate (FDR) < 0.05]. All seven miRNAs remained to be significantly associated with urinary arsenic after adjusting for creatinine, and five of the seven miRNAs were also associated with arsenic in plasma. Enrichment analysis showed that the identified miRNAs may be involved in cancer-related pathways.[¤]CONCLUSIONS[|]We identified and validated miRNAs associated with arsenic exposure in populations with high and common exposure levels.[¤]