In conclusion, the present study highlights the role of CBP/p300 in driving a redox/autophagy axis leading to senescence-induced growth arrest in non-small cell lung cancer cells and brings novel insight into the regulation of cellular pathways controlled by a major acetyltransferase family, i.e., p300/CBP, in lung cancer cells, involving acetylation, ROS formation, DNA damage, autophagy, and senescence activation. Here, EP300 is linked to lung cancer.