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A correlation between protein damage and death, but not DNA damage, was found among cells from robust and standard bacterial and invertebrate species. However, the bottleneck in DNA repair efficacy appears more at the level of proteome damage than DNA damage. Here we present a comparative study of SW480 cells derived from a primary colon adenocarcinoma and SW620 metastatic cells derived from the same primary tumor and provide evidence that correlation between death and proteome damage extends to human tumor cells. A higher resistance of SW620 cells, compared to SW480, to killing by UVC light correlates with reduced levels of incurred irreversible oxidative protein damage (carbonylation) related to lower levels of ROS and of proteins intrinsically susceptible to oxidative damage due to imperfect folding. This study provides a concept for sensitizing tumor cells to cancer therapies and assessment of cancer cell fitness.