Abstract: In order to provide evidence for resistance breeding scheme, the major gene of resistance to tobacco bacterial wilt was analyzed. The individual plants of 19 tobacco F2 populations were identified in disease field of Anhui Province in China in 2010 and mixed inheritance model (single-step-method) was used. The results showed that the inheritance of the resistance to tobacco bacterial wilt accorded with the major genes model which was additive - dominant - epistasis model (B-1 model) or additive - dominant model (B-2 model). The value of generalization heritability of major genes was among 52%-97%. The effect value order of major gene types was AABB ≥ AABb ≥ AAbb ≥ AaBB ≥ AaBb ≥ Aabb ≥ aaBB ≥ aaBb ≥ aabb. The epistasis effect was existed among major genes.