Background <p>Esophageal squamous cell carcinoma (ESCC) ranks among the most lethal malignant neoplasms globally, representing a significant risk to public health.</p> Objectives <p>This study investigates the impact of lncRNA ADAMTS9-AS1 on the function of ESCC cells by targeting and regulating miR-575/CADM2 axis.</p> Materials and methods <p>qPCR was employed to assess the expression of ADAMTS9-AS1, miR-575, and CADM2 in ESCC tissues and cells. Chi-square test was utilized to examine the association between ADAMTS9-AS1 and clinical indicators. Cox model was applied to identify risk factors of poor prognosis, and survival curves were generated using the Kaplan-Meier method. Furthermore, the effects of overexpressing ADAMTS9-AS1 alone and in conjunction with miR-575 were analyzed in ESCC cell lines, utilizing CCK-8 assays to evaluate cell proliferation, and Transwell assays to assess cell invasion and migration capabilities.</p> Results <p>The study revealed that in ESCC tissues and cell lines, the expression levels of ADAMTS9-AS1 and CADM2 were decreased and exhibited a positive correlation, whereas the miR-575 was elevated and demonstrated a negative correlation with both molecules. The expression of ADAMTS9-AS1 was associated with TNM staging and lymph node metastasis, serving as a risk factor for poor prognosis. Overexpression ADAMTS9-AS1 could inhibit miR-575 expression, and suppress cellular proliferation, migration, and invasion. However, this inhibitory effect was reversed when miR-575 was concurrently overexpressed.</p> Conclusion <p>The targeting effect of ADAMTS9-AS1 on miR-575/CADM2 changes in ESCC cell function and further mediated the progression of ESCC. ADAMTS9-AS1 has the potential to be a prognostic biomarker and molecular target for ESCC.</p>