Ankylosing spondylitis (AS) is an insidious and debilitating form of arthritis that involves the axial skeleton, and its etiology and pathogenesis remain unclear. In the present study, three patients with AS and three normal controls from our hospital were enrolled. RNA sequencing and bioinformatics analysis were performed in order to identify the differentially expressed (DE) mRNAs (DEmRNAs) and DE long non‑coding RNAs (DElncRNAs) between the patients with AS and normal controls. Construction of an AS‑specific protein‑protein interaction network, a weighted DElncRNA‑DEmRNA co‑expression network and functional annotation of the DEmRNAs co‑expressed with DElncRNAs was performed. Nearby cis‑targeted DEmRNAs or DElncRNAs were identified by searching for DEmRNAs that were transcribed within 100‑kb up‑ or downstream of DElncRNAs. Based on the Gene Expression Omnibus datasets GSE25101 and GSE73754, the expression of selected DEmRNAs and DElncRNAs were verified using published RNA sequencing data from blood samples, and receiver operating characteristic analysis of selected DEmRNAs was performed. Compared with the normal controls, 1,072 DEmRNAs and 372 DElncRNAs in the patients with AS were identified. Caspase recruitment domain family member 11 and DNA methyltransferase 1 have great diagnostic value for AS. MSTRG.8559 and LINC00987 were also identified as two hub DElncRNAs. The T‑cell receptor signaling pathway was a significantly enriched pathway of the DEmRNAs co‑expressed with DElncRNAs in patients with AS. In conclusion, the present study identified the key DEmRNAs and DElncRNAs in AS, which provides novel information for understanding the pathogenesis of AS and developing potential biomarkers for AS.