The major findings of this study were as follows: (1) ZNF143 knockdown protected cancer cells from cell death under metabolic stress in breast cancer; (2) cell survival by ZNF143 knockdown under metabolic stress was dependent on chloroquine, an inhibitor of the autophagic process; (3) ZNF143 knockdown altered proteins related to the autophagic process; (4) the p53–NQO1 axis was related to ZNF143 expression; and (5) according to the TCGA cohort, ZNF143 mRNA expression was related to disease-free survival of breast cancer patients. This evidence concerns the gene ZNF143 and cancer.