Tuberculosis (TB) remains one of the world’s deadliest communicable diseases. In 2013, an estimated 9 million people developed TB and 1.5 million died from the disease. In this research we studied the bioactive compounds of flavonoid-RNA Polymerase receptor interactions In silico. First, homology modeling was performed to obtain the three dimensional structure of RNA Polymerase Mycobacterium tuberculosis and preparation of sixth bioactive compounds of flavonoid which will be as ligands with rifapentine as a comparison. The sixth bioactive compounds of flavonoid and rifapentine were docked with beta subunit of RNA polymerase Mycobacterium tuberculosis until energy binding values were obtained. The sixth bioactive compounds of flavonoid, and rifapentine were docked with software PLANTS. The sixth bioactive compounds of flavonoid, and rifapentine binds to active site on the β-subunit RNA polymerase, the mechanism model for inhibition of RNA polymerase in which sixth bioactive compounds of flavonoid and rifapentine sterically block synthesis of an RNA product longer than three nucleotides (“steric-occlusion model”) Result : Luteolin and Rutin had lesser energy binding values than rifapentine and luteolin and rutin also predicted to have greater binding affinity to RNA polymerase Mycobacterium tuberculosis Keywords: Tuberculosis, RNA polymerase, Flavonoids, Antituberculosis, Docking