Six populations (P1,P2,F1,B1,B2 and F2) were constructed from the resistant variety Taiyan 7 as the female parent and the susceptible variety NC89 as the male parent. The inheritance of the tobacco powdery mildew was investigated by the mixed major-gene plus polygene inheritance model. It was found that the inheritance of the resistance to tobacco powdery mildew was fit to a mixed genetic model of two major genes with additive-dominant-epistatic effects plus polygenes with additive-dominant-epistatic effects(the E-0 model).The heritability of major gene in B1, B2 and F2 was 88.05%, 32.62% and 84.43%, respectively. Because of the high heritability of the major gene, the selection of resistant plant could be carried out in the early breeding for disease resistance. Both of the polygene heritabilities in B1, F2 were 0.00%,which showed that the environmental effect should also be taken into consideration for the outbreak of tobacco powdery mildew.