The present invention discloses benzofuran and Coumestans derivatives represented by the formulas (I), (II), (III), (IV), a preparation method thereof, and a use of the benzofurans and Coumestans derivative compounds in the treatment of multidrug-resistant tuberculosis diseases. The benzofuran and Coumestans derivatives of the present invention are a type of anti-mycobacterium tuberculosis compound having novel structure and remarkable antibacterial effect, which uses polyketide synthase encoded by the pks13 gene fragment of mycobacterium tuberculosis as target, inhibiting the growth and reproduction of microorganisms, especially inhibiting the synthesis of mycolic acid in the cell wall of mycobacterium tuberculosis. It has potential application prospects in the medicine field.