Objective <p>Endometrial carcinoma (EC) ranks among the three most prevalent malignant tumors affecting the female reproductive system. DEPDC1-AS1 is a newly identified lncRNA, and its mechanism of action in EC remains to be explored.</p> Methods <p>100 hyperplasia and 100 EC patients were included. The abundance of DEPDC1-AS1, miR-508-3p, and SQSTM1 was quantified by qRT-PCR. Kaplan–Meier survival curve and Cox regression predicted prognostic factors. Pearson correlation was used to assess the relationships among the molecular markers. Cell proliferation was assessed with the CCK-8 assay, and migration/invasion with Transwell assays. The regulatory interactions were predicted by bioinformatics and validated through dual-luciferase reporter assays and co-transfection experiments.</p> Results <p>DEPDC1-AS1 was enhanced in EC tissues and cell lines and identified as an independent prognostic factor. Its expression was associated with FIGO stage and cervical invasion, while lower DEPDC1-AS1 levels correlated with improved survival outcomes. Functional experiments showed that silencing DEPDC1-AS1 inhibited EC cell proliferation, migration, and invasion. Mechanistically, DEPDC1-AS1 sponges miR-508-3p, with a confirmed negative correlation between the two. DEPDC1-AS1 promoted EC cell aggressiveness by modulating miR-508-3p, which directly targets SQSTM1. SQSTM1 expression was negatively correlated with miR-508-3p and positively correlated with DEPDC1-AS1.</p> Conclusion <p>DEPDC1-AS1 may serve as a promising prognostic biomarker in EC. These findings suggest that DEPDC1-AS1 facilitates EC progression through the miR-508-3p, highlighting its potential as a therapeutic target.</p>