ObjectiveThis study aimed to identify long non-coding RNAs (lncRNAs) that could serve as prognostic biomarkers for non-small cell lung cancer (NSCLC).MethodsThe Encyclopedia of RNA Interactomes (ENCORI) database was used to analyze the expression profile and RNA interaction network of lncRNA SNHG4 in NSCLC. Cell experiments were performed to determine the effects of lncRNA SNHG4 on the proliferation and migration of lung cancer cell line A549. The dual-luciferase reporter assay was employed to validate the interaction between SNHG4 and its potential targets.ResultslncRNA SNHG4 was highly expressed in NSCLC tissues. Kaplan-Meier survival analysis showed that patient survival rate was significantly correlated with SNHG4 expression levels. Knockdown of SNHG4 inhibited the proliferation, migration, and invasion of NSCLC cells while promoting cell apoptosis. Mechanistic studies identified miR-409-3p and DDX5 as direct targets of SNHG4. SNHG4 downregulated miR-409-3p expression in NSCLC cells, thereby relieving the inhibitory effect of miR-409-3p on DDX5 and promoting NSCLC cell growth. ConclusionlncRNA SNHG4 may exert its tumor-promoting role in NSCLC through the lncRNA SNHG4/miR-409-3p/DDX5 signaling pathway.