Background <p>Gastric cancer (GC) remains a formidable threat to global health. Although SOCS2-AS1 is abnormally expressed in various cancers, its precise function and operational mechanisms in the context of GC have not been fully elucidated.</p> Methods <p>This study collected 102 pairs of GC and adjacent normal tissue samples and cultured multiple GC cell lines. SOCS2-AS1, miR-324-3p, and glutamate ionotropic receptor kainate type subunit 3 (GRIK3) expression were detected by qRT-PCR. Bioinformatics analysis was performed using databases such as GEPIA and Starbase. Functional experiments including CCK-8 assay and Transwell assay were conducted to evaluate cellular functions. Subcellular localization was determined using nuclear-cytoplasmic separation technology. Direct molecular interactions were validated via dual luciferase reporter assays.</p> Results <p>The downregulation of SOCS2-AS1 in GC tissues and cell lines is significantly associated with an unfavorable patient prognosis. Overexpression of SOCS2-AS1 markedly suppressed GC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) progression. Mechanistic studies revealed that SOCS2-AS1 targets miR-324-3p. and re-expression experiments confirmed its ability to reverse the anti-cancer effects of SOCS2-AS1. GRIK3 was identified as a direct downstream target of miR-324-3p. Ultimately, SOCS2-AS1 exerts its tumor-suppressive function through the miR-324-3p/GRIK3 axis.</p> Conclusion <p>This research identifies SOCS2-AS1 as an anti-cancer lncRNA in GC and uncovers its mechanism of action via the SOCS2-AS1/miR-324-3p/GRIK3 axis in suppressing tumor progression. Thus, SOCS2-AS1 may serve as a potential diagnostic biomarker and therapeutic target for GC.</p>