Abstract: Objective To investigate the role of long non-coding RNAs （lncRNAs） in the incidence and progression of diabetic nephropathy （DN）. Methods The differentially-expressed lncRNAs and mRNAs in the kidney biopsy specimens were detected by RNA-seq sequencing between the DN and normal control groups （NC）. The biological functions of differentially-expressed mRNAs were analyzed through the GO and KEGG databases, and the interaction among differentially-expressed lncRNAs and mRNAs was analyzed through co-expression network analysis. The relative expression levels of target lncRNAs and mRNAs in DN kidney tissues were detected by real-time fluorescent quantitative PCR （qRT-PCR）. Results RNA-seq sequencing results showed that a total of 353 differentially-expressed lncRNAs in the DN group compared with that in the NC group, in which 224 were up-regulated and 129 were down-regulated. qRT-PCR revealed that the relative expression levels of CRNDE, PVT1 and BLZF2P in the DN group were significantly higher （all P < 0.001）, whereas the relative expression levels of WT1-AS, TARID and ST13P6 were remarkably lower than those in the NC group （all P < 0.001）. Moreover, co-expression network analysis and bivariate correlation analysis demonstrated that lncRNA CRNDE was negatively correlated with NPHS1 （the encoded nephrin is the decisive key protein for the structural integrity and function of podocytes）. Conclusions The expression level of lncRNA CRNDE is significantly up-regulated in DN patients, which is negatively correlated with NPHS1, indicating that lncRNA CRNDE may promote the podocyte damage in DN by regulating the expression level of NPHS1.