Abstract: Ankylosing spondylitis (AS) is a chronic inflammatory disease that results in severe pain and stiffness in the joints. The causes and pathophysiology of AS are still largely unknown. The lncRNA H19 plays key roles in the pathogenesis of AS by mediating inflammatory progression by acting in the axis of IL-17A/IL-23. The aims of this study were determining the role of lncRNA H19 in AS and assessing its clinical correlation. A case–control study was conducted and qRT-PCR was utilized to measure H19 expression. Comparing AS cases to healthy controls, it was found that H19 expression was significantly upregulated. For AS prediction, H19 demonstrated a 81.1% sensitivity, 100% specificity, and 90.6% diagnostic accuracy at a lncRNA H19 expression value of 1.41. lncRNA H19 had a significantly positive correlation with AS activity, MRI results, and inflammatory markers. lncRNA H19 seemed to be an independent predictor of AS (adjusted OR of 211 (95% CI: 4.7–939; p = 0.025)). After 3 months of clinical follow-up, seventeen patients (32.1%) showed minimal clinical improvement and fifteen patients (28.3%) showed major improvement. AS activity scores were significantly decreased in patients with high H19 expression. A significantly elevated lncRNA H19 expression was observed in AS cases compared with that in healthy controls. These results suggest that upregulation of lncRNA H19 expression may be involved in the pathogenesis of AS. The expression of the lncRNA H19 is related to the duration and activity of the disease. LncRNA H19 expression seems to be an independent predictor of AS.