In summary, our results revealed that SFN-Cys with longer half-life in circulation induced apoptosis in A549 and SK-1 cells via persistently activated ERK1/2, upregulating maspin and Bax, and downregulating Bcl-2 and α-tubulin, ultimately leading to the activation of caspase-3 in NSCLC cells. Here, MAPK3 is linked to non-small cell lung carcinoma.