In this paper, bacterial wilt resistant variety Xanthi and susceptible variety Samsun, their F1s and F2s were used to study inheritance of resistance of oriental tobacco to bacterial wilt. These populations and their individuals were planted in identifying field of Fujian Province. The identified data of individuals was analyzed using major gene plus poly-gene mixed inheritance model. Results indicated that the resistance to bacterial wilt in oriental tobacco was controlled by two independent major genes with additive-dominance-epistatic effects plus polygenes with additive-dominance effects (the E-1 model). Heritability value of the major genes reached 49.63%.