Abstract: To address the challenge of a single-dose, single-target vaccine being unable control multiple tobacco viral diseases simultaneously, we constructed six recombinant viruses that exhibit strong cross-protection effective, stably existence in Nicotiana benthamiana and simultaneously resistance to CMV, TMV, PVY and TVBMV. These recombinant viruses all used the cucumber mosaic virus Fny (CMV_Fny) strain as the vaccine vector, with conserved combination fragments of TMV, PVY and TVBMV genomes inserted into the CMV_Fny RNA2 attenuated mutant in different permutations. The relative control efficacy of the six recombinant viruses exceeded 87% against CMV infecting alone, ranging from 22.2% to 46.2% against single infections of the other three viruses, and from 16% to 37% against mixed infections of all four viruses. This study provides vaccine candidates for controlling tobacco virus diseases and enriches the practice of creating attenuated plant virus vaccines.