<p>EGFR and HER2 are overexpressed in numerous malignancies, including breast cancer. A novel series of 1,2,3-triazole hybrids comprising quinoline-imidazole moieties was created as part of an ongoing endeavor to find new anticancer drugs targeting these proteins. Several analytical techniques, such as ¹H-NMR, ¹³C-NMR and ESI-MS, corroborated the newly produced compounds. Using doxorubicin as a reference, the compounds were evaluated for their anticancer activity against the human cancer cell lines MCF-7 and HepG2. The o-methoxy (<b>7e</b>) and p-acetyl (<b>7j</b>) substituted analogs exhibited the highest activity against MCF-7 cell lines, with IC₅₀ values of 0.473 ± 0.05 and 0.496 ± 0.04 µM, respectively, while the o-chloro (<b>7c</b>) and o-methoxy (<b>7e</b>) substituted analogs exhibited the highest activity against the HepG2 cell line, with IC₅₀ values 0.758 ± 0.06 and 0.831 ± 0.07 µM respectively.As a result, substances with significant anti-proliferative activity were submitted to an EGFR/HER2 kinase assay. Molecular docking studies done on EGFR and HER2 proteins demonstrated the molecules’ high binding affinity. The projected ADME features of substances indicate that they possess the most drug-like qualities.</p> Graphical Abstract <p></p>