Lung Cancer (LC) is the leading cause of cancer deaths globally. Long non-coding RNAs (lncRNAs) have emerged as important regulators in lung cancer, playing key roles in tumor development and metastasis. Recent advances in nanoparticle-based drug delivery systems and lncRNA research offer promising strategies to enhance treatment efficacy and reduce adverse effects. CS/AuNPs were synthesized via chloroauric acid reduction in chitosan solution, and DOX was incorporated using TPP crosslinking to form CS/AuNP-DOX. The nanoparticles were characterized by FT-IR spectroscopy, particle size, and zeta potential analysis. The in vitro effects of CS/AuNP-DOX on cytotoxicity (IC50), apoptosis, cell cycle, and lncRNA expression were evaluated. CS/AuNP-DOX demonstrated enhanced anticancer activity compared to free DOX, with reduced IC₂⁽ (1.36 μM vs. 1.9 μM), increased apoptosis (57% vs. 37%), and greater G2/M phase cell cycle arrest. Importantly, CS/AuNP-DOX induced only limited apoptotic and cell-cycle effects in normal cells (HFFF2). Additionally, treatment with CS/AuNP-DOX significantly downregulated the expression of HIF1A-AS1 and DLGAP1-AS2. The enhanced therapeutic efficacy and reduced toxicity observed in this study suggest that CS/AuNP-DOX may overcome limitations of conventional chemotherapy by improving drug bioavailability. These findings highlight the potential of integrating nanoparticle-based drug delivery with lncRNA-targeted therapies to improve lung cancer treatment. However, further in vivo studies are required to confirm these results.