The invention belongs to the field of pharmaceutical chemistry, and particularly discloses 7-fluoro-substituted Isaindigotone derivatives. The structural formula of the derivatives is disclosed as Formula (I) or Formula (II), wherein X is C or N; R1 is hydrogen, amino, substituted amino, orpenta- or hexa-heterocyclic radical; R2 is hydrogen, hydroxy, amino, C1-C8 alkyl, or C1-C8 alkoxy or halo; R3, R5 and R6 are defined the same as R2; and R4 is hydrogen, hydroxy, amino, phenyl, C1-C8 cycloalkyl, C1-C8 alkyl, C1-C8 alkoxy, C1-C6 alkyl acyloxy, C1-C6 alkynyl, halo, or penta- or hexa-heterocyclic radical. The fluoro-substituted Isaindigotone derivatives can bebondedwith NM23-H2 protein and block the interaction between the NM23-H2 protein and c-myc G-quadruplex DNA, thereby causing the reduction of protooncogene c-myc transcription and translation, and inhibiting the proliferation of multiple tumor cell strains. The fluoro-substituted Isaindigotone derivatives have wide antitumor effects. The fluoro-substituted Isaindigotone derivatives are a novel NM23-H2-protein-targeted transcription regulation blocker, and have wide application space in preparing anticancer drugs.