The capacity of esculetin to prevent cancer has been linked to the regulation of multiple proteins, including Bcl‐2, Bcl‐xL, Bax, Bak, Bid, caspases,3, 7, 8, 9, 12 cyclins (B1, D1, E) and CDKs,2, 4, 6 p21, p27, p53, and p27KIP, VEGF, GRP‐78, PERK, MMP‐2, MMP‐7, PARP, Nrf‐2, Ki‐67, pRB, N‐cadherin, E‐cadherin, survivin, sp1, JAK2/STAT3, cyto‐chrome‐C, NF‐κB, NF‐κBp65, NF‐κBp50, Wnt/β‐catenin, IL‐6, TNF‐α, phosphorylated‐Akt, PI3K/Akt, MAPK, Raf/MEK/ERK. This evidence concerns the gene TP53 and cancer.