<p>The objective of this research was to explore the impact of HOXC13-AS on the prognosis of NSCLC patients and the mechanism underlying disease progression. The study included 124 NSCLC patients. The expression levels of HOXC13-AS and miR-218-1-3p in NSCLC tissues and cells were assessed by RT-qPCR. The cumulative survival of NSCLC patients was examined by the Kaplan-Meier method. Cell viability was determined by MTT. Transwell was adopted to evaluate the migration and invasion capabilities of the cells. The interaction between HOXC13-AS and miR-218-1-3p was verified by luciferase reporter assay and RIP assay. Pearson correlation coefficient was utilized to assess the relationship between HOXC13-AS and miR-218-1-3p. HOXC13-AS was elevated in NSCLC tissues and cells, and patients with high HOXC13-AS expression had poorer cumulative survival than the low expression group. Silencing of HOXC13-AS led to a decrease in HOXC13-AS expression and inhibition of cell proliferation, migration and invasion in cells. Experiments confirmed that HOXC13-AS targets miR-218-1-3p. miR-218-1-3p was downregulated in NSCLC tissues and cells, and HOXC13-AS was negatively correlated with miR-218-1-3p. After silencing HOXC13-AS, further inhibition of miR-218-1-3p led to a decrease in its levels and enhanced cell proliferation, migration, and invasion. In NSCLC patients, HOXC13-AS is aberrant expression and closely associated with poor prognosis. Inhibition of miR-218-1-3p expression partially reverses the inhibitory effects of HOXC13-AS silencing on NSCLC cells. This suggests that HOXC13-AS could serve as a promising biomarker for NSCLC, providing new insights into NSCLC progression.</p>