Ulcerative colitis (UC) is a major type of inflammatory bowel disease (IBD), which is characterized by diffuse inflammation of the mucosa of the colon and rectum. Abdominal pain, diarrhea, and hematochezia are UC’s main clinical manifestations. Pathogenesis of UC has not yet been clearly elucidated, but it is considered to result from dysregulated expressions of molecules engaged in proinflammatory and anti-inflammatory processes. CXCL8 is one of the most important proinflammatory factors which play a vital role in many inflammatory diseases including UC. The CXCL8-CXCR1/2 axis participates in the pathogenesis of UC through multiple signaling pathways, including PI3k/Akt, MAPKs and NF-κB signaling pathways. Meanwhile, more and more studies in recent years have shown that UC patients have specific non-coding RNA (ncRNA) expression profiles, which may be involved in the occurrence and development of inflammation. In this article, we analyzed the CXCL8-CXCR1/2 axis related signaling pathways and ncRNAs in UC, as well as recent advances in our understanding of the CXCL8-CXCR1/2 axis inhibition as a therapeutic strategy against UC.