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. The gene discussed is NFKB1; the disease is cancer.