Background <p>Bladder cancer (BLCA) represents one of the most prevalent malignant neoplasms within the urinary system, and its incidence is progressively rising annually in China.</p> Objectives <p>This research investigated the clinical significance of DLGAP1-AS2, and examined its potential mechanisms in modulating the behavior of BLCA cells.</p> Methods <p>This study collected cancerous and normal tissue samples from 86 BLCA patients. qPCR was employed to assess DLGAP1-AS2 and miR-451a expression. Chi-square test was utilized to analyze the correlation between DLGAP1-AS2 and clinical parameters. Cox model and Kaplan-Meier analysis were conducted to evaluate the association between DLGAP1-AS2 and the prognosis of BLCA patients. Furthermore, DLGAP1-AS2 was silenced, both independently and jointly with miR-451a, in BLCA cell lines. CCK-8 assay assessed cell proliferation, and the Transwell assay evaluated cell migration and invasion capabilities.</p> Results <p>DLGAP1-AS2 was elevated in BLCA tissues and exhibited a correlation with both smoking history and pathological features in BLCA patients. DLGAP1-AS2 was identified as a prognostic risk factor, wherein patients exhibiting low expression had a more favorable prognosis. DLGAP1-AS2 was up-regulated in BLCA cells, and its silencing led to a reduction in the proliferation, migration, and invasion of BLCA cells. Conversely, miR-451a was down-regulated in BLCA tissues and cells, and it demonstrated a negative regulatory interaction with DLGAP1-AS2. The concurrent silencing of DLGAP1-AS2 and miR-451a effectively restored the biological behaviors of BLCA cells.</p> Conclusion <p>DLGAP1-AS2 is a potential biomarker for evaluating the severity of BLCA and for predicting clinical prognosis. DLGAP1-AS2 regulates the malignant progression of BLCA via miR-451a.</p>