​This study introduces a pioneering approach in cancer therapy via the green synthesis of 1,2,4-triazole chromene derivatives, utilizing a magnetically recyclable nanocatalyst. A core-shell MFe₂O₄@Piperazine magnetic nanocatalyst (MNPs) was synthesized and thoroughly characterized through FT-IR, XRD, EDS, FESEM, TEM, and VSM analyses, confirming its efficient catalytic activity. The nanocatalyst enabled a one-pot, multicomponent Knoevenagel-condensation-cyclization cascade reaction under eco-friendly conditions, yielding a library of 1,2,4-triazole chromene hybrids (7a-i and 8a-i). These hybrids demonstrated significant antiproliferative effects against A549, MCF-7, and HepG2 cancer cell lines. Notably, compounds 7e and 8e, containing a 3,4,5-trimethoxy pharmacophore, exhibited potent cytotoxicity against MCF-7 breast cancer cells (IC50: 1.21 and 1.02 μM, respectively), surpassing the clinical reference drug, etoposide (Etoposide). Importantly, these compounds displayed high cancer cell selectivity with minimal toxicity to normal L929 cells. Mechanistic studies confirmed a dual-action pathway involving apoptosis induction and microtubule destabilization. This research not only presents a sustainable synthesis platform for bioactive compounds but also identifies promising anticancer leads, paving the way for advancements in cancer therapeutics​