Abstract: ob＜x＞jective at present, many gene association studies have identified the genes related to the susceptibility of ankylosing spondylitis (ankylosing spondylitis, AS), but these methods provide little information about the changes of gene activity in the course of the disease. The purpose of this study is to identify candidate genes related to AS through bioinformatics analysis, and to provide potential diagnostic markers and therapeutic targets for AS. Methods The original data sets of GSE25101, GSE41038 and GSE73754 were downloaded from (Gene ex＜x＞pression Omnibus, GEO), a comprehensive databa＜x＞se of gene ex＜x＞pression. Three groups of microarrays were used to screen the differentially expressed genes ((differentially expressed genes, DEGs) between AS and normal samples. Then DEGs gene ontology (Gene Ontology, GO) functional annotation, Kyoto Encyclopedia of Gene and Genome ((Kyoto Encyclopedia of Genes and Genomes, KEGG) signal pathway enrichment analysis and KEGG disease enrichment analysis were carried out, and the real core pathway was obtained by the intersection of the three enrichment Results Construct the PPI network, screen the core genes respectively, verify the intersection of the three core genes, and get the real key genes. Results the enrichment of GO was mainly related to the immune process of T cells. The results of KEGG enrichment are mainly related to cancer pathway, me＜x＞tabolic pathway, PI3K-Akt signal pathway, regulation of actin cytoskeleton, Th17 cell differentiation and Th1 and Th2 cell differentiation. KEGG disease enrichment results showed that differential genes were mainly involved in immune system diseases, me＜x＞tabolic diseases and skeletal muscle diseases. PPI core gene screening found that the highest correlation degree of TP53 and the intersection of three chips to get RUNX3, IL2RB and RPL17. Conclusion Immune and me＜x＞tabolic abnormalities play an important role in the pathogenesis of AS. PI3K-Akt signaling pathway, Th17 cell differentiation and Th1 and Th2 cell differentiation may be important signal pathways in the development of AS. TP53, RUNX3, IL2RB and RPL17 may be potential key genes and biomarkers of AS