Mechanistically, L14‐8 binds to and promotes the ubiquitin‐mediated PLK1 degradation, resulting in an increase of downstream TP53 protein phosphorylation, which is further enriched at the promoter of SAT1, a well‐established ferroptosis inducer, and boosting SAT1 transcription thus triggers ferroptosis‐mediated cancer cell death. This evidence concerns the gene TP53 and cancer.