In the present study, we have demonstrated for the first time that (a) CDDP down-regulates EGFR, activates p53 and increases ROS production in chemosensitive but not in chemoresistant NSCLC; (b) Akt confers resistance in NSCLC in part by activating EGFR and down-regulating p53 and ROS production, and (c) p53 activation inhibits EGFR signaling and increases ROS production. Here, EGFR is linked to non-small cell lung carcinoma.