The E3 ligase Skp2 influences the levels of necroptosis regulator MLKL, and Skp2-inhibition sensitizes non-small cell lung cancer (NSCLC) cells to cisplatin in vitro and in vivo, suggesting Skp2 as a therapeutic target to overcome NSCLC chemoresistance. This evidence concerns the gene MLKL and non-small cell lung carcinoma.