<p>Casein kinase 2 (CK2) is a key regulator of cancer cell survival and proliferation, making it an attractive therapeutic target. Quinalizarin is a potent CK2 inhibitor; however, its clinical application is limited by suboptimal delivery and bioavailability. This study aimed to develop and characterize a quinalizarin–gold nanoparticle nanocomplex (QGNPs) and evaluate its potential to enhance anticancer activity in non-small cell lung cancer (NSCLC). QGNPs were synthesized using sulfhydryl calcium acetate as a linking agent. The nanocomplex was characterized by UV–Vis spectroscopy, dynamic light scattering, zeta potential analysis, and transmission electron microscopy. Drug loading and release profiles were assessed using UV–Vis spectroscopy. In vitro cytotoxicity was evaluated in A549 lung cancer cells using MTT assay, and cellular uptake was examined by confocal laser scanning microscopy. QGNPs demonstrated successful conjugation, with an increase in particle size from ~ 15 to 85.18 ± 8.25 nm and a zeta potential shift to − 19.59 ± 5.62 mV. The nanocomplex exhibited pH-responsive drug release, with significantly higher quinalizarin release under acidic conditions (pH 5.0) compared to physiological pH (7.4). In vitro studies showed that QGNPs significantly enhanced cytotoxic activity compared to free quinalizarin, with lower IC₅₀ values. Confocal microscopy confirmed efficient intracellular uptake of QGNPs in A549 cells. QGNPs represent a promising nanocarrier system for improving the delivery and anticancer efficacy of quinalizarin in NSCLC. The enhanced cytotoxicity and pH-responsive release suggest potential for targeted cancer therapy. However, further studies are required to elucidate underlying mechanisms and to evaluate radiosensitization and in vivo therapeutic efficacy</p>