The present study, for the first time, reports the significance of G4 motifs in the 5′UTR of a key tumor suppressor, which uncovers a novel mechanism that G4-stabilizing compounds may cause cytotoxicity to normal cells: those compounds may also target on the G4 motifs within the 5′ UTRs to inhibit the protein expression of certain master regulators of cellular physiology (such as P1-HNF4α and other LETFs). The gene discussed is HNF4A; the disease is neoplasm.