We provided the first evidence that miR-155 mediated a high level of ATO-resistance in a lung cancer cell line, A549R cells by suppressing cellular apoptotic activities and upregulating the expression of antioxidants NQO1 and HO-1 via activation of the Nrf2 signaling pathway (Figs 2–6), and this subsequently protected A549R cells from ATO-induced apoptotic cell death, thereby promoting cell survival (Figs 4 and 5). Here, NFE2L2 is linked to lung cancer.