As we further tested the role of USP10 in cisplatin sensitivity in a large panel of NSCLC cell lines, surprisingly, we discovered that upon cisplatin treatment the depletion or inhibition of USP10 could lead to two entirely different outcomes: cell survival or apoptosis, depending on the cellular status of TP53—USP10 promotes cisplatin sensitivity in wild-type p53 cells, while USP10 confers cisplatin resistance in mutant p53 cells. Here, TP53 is linked to non-small cell lung carcinoma.