Our findings showed that: (i) lung cancer cell cultures exhibited higher resistance to cisplatin in hypoxic than in normoxic conditions; (ii) upon exposure to hypoxic conditions, lung cancer cells escaped from cisplatin-induced senescence, which relied on the p53/p21 signaling pathway; and (iii) autophagy inhibition by HCQ reduced escape from senescence of CIS-treated lung cancer cells in hypoxia. This evidence concerns the gene TP53 and in situ carcinoma.