Background MicroRNAs (miRNAs) are endogenous noncoding RNAs of approximately 22 nucleotides in length that mediate post-transcriptional gene silencing by annealing to sequences in the 3-untranslated region of target mRNAs.The study presented herein focused on differentially expressed miRNAs and their targets in VSD patients.Methods In this study, we analyzed 30 candidate miRNAs selected based on microarray data for cardiac tissue from individuals with congenital heart defects (CHDs).To identify specific miRNA characteristic of VSD patients, we compared the expression levels of these 30 candidate miRNAs in cardiac tissue from VSD patients (n=40) to the expression levels in cardiac tissue from healthy individuals (n=9) using real-time PCR.Then we used bioinformatics tools to search for the target genes of specific miRNAs (rniR-1-1 and miR-18 1 c) and measured their expression levels with real-time PCR.Target genes of miR-1-1 were EGFR, GJA1, MED1, TGFBR3, SOX9, CITED2, EDN1, PAX3, RARB, SMAD2, SRI.Target genes of miR-181c were SEMA3C, ACVR2B, ADM, ADRBK1, COL5A1, SMAD7, PDGFRA, VCAM1, BMPR2, NF 1, HAND2.Lastly, to evaluated the interaction between miR-1-1 and miR-18 1 c with their predicted target genes, we conducted luciferase assay, immunohistochemistry and vitro assays of H9C2 rat cardiac fibroblasts of target genes.Results This study identified specific changes in the miR-1-1 and miR-181c levels in human cardiac samples from individuals with ventricular septal defects (VSDs) relative to the levels in healthy control tissue.Increased levels of GJA1 and SOX9 were associated with the decreased expressionof miR-1-1 in VSD patients, and increased miR-181c expression was correlated with down regulated BMPR2 levels.In addition, the results revealed that miR-1-1 and miR-181c directly regulate the expression of these predicted targets.Conclusions miR-1-1 and miR-181 c are associated with the pathogenesis of VSDs.