AimTo evaluate the expression profile of long non-coding RNAs (lncRNAs) in calcific aortic valve disease (CAVD) and explore their potential mechanism of action.MethodsThe gene expression profiles (GSE153555, GSE148219, GSE199718) were downloaded from the Gene Expression Omnibus (GEO) database and FastQC was run for quality control checks. After filtering and classifying candidate lncRNAs by differentially expressed genes (DEGs) and weighted co-expression networks (WGCNA) in GSE153555, we predicted the potentialcis-ortrans-regulatory target genes of differentially expressed lncRNAs (DELs) by using FEELnc and established the competitive endogenous RNA (ceRNA) network by miRanda, more over functional enrichment was analyzed using the ClusterProfiler package in R Bioconductor. The hubcis-ortrans-regulatory genes were verified in GSE148219 and GSE199718 respectively.ResultsThere were 340 up-regulated lncRNAs identified in AS group compared with the control group (|log2Fold Change| ≥ 1.0 and Padj≤ 0.05), and 460 down-regulated lncRNAs. Based on target gene prediction and co-expression network construction, twelve Long non-coding RNAs (CDKN2B-AS1, AC244453.2, APCDD1L-DT, SLC12A5-AS1, TGFB3, AC243829.4, MIR4435-2HG, FAM225A, BHLHE40-AS1, LINC01614, AL356417.2, LINC01150) were identified as the hubcis-ortrans-regulatory genes in the pathogenesis of CAVD which were validated in GSE148219 and GSE19971. Additionally, we found thatMIR4435-2HGwas the top hubtrans-acting lncRNA which also plays a crucial role by ceRNA pattern.ConclusionLncRNAs may play an important role in CAVD and may provide a new perspective on the pathogenesis, diagnosis, and treatment of this disease. Further studies are required to illuminate the underlying mechanisms and provide potential therapeutic targets.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12872-023-03311-x.