Abstract: The tobacco-grain intercropping system plays a vital role in ensuring both food security and tobacco production. However, herbicide residues from preceding crops like corn and soybean can readily cause phytotoxicity in tobacco, posing a significant constraint to the sustainable development of leaf tobacco. To clarify the impact of different types of herbicide residues on the growth and development of tobacco. Phytotoxicity symptoms on tobacco seedlings were observed, and plant height, leaf area, root volume, and root activity were measured through indoor pot experiments and field plot trials. A first-order kinetic model was employed to fit the dissipation dynamics of soil residues. The field safe application interval was estimated by combining these dynamics with the phytotoxicity threshold. Tobacco exhibited high sensitivity to nicosulfuron, mesotrione, pendimethalin, and atrazine. At recommended application rates, these herbicides significantly inhibited seedling height, inducing typical symptoms including albino/yellowing of new leaves, leaf wrinkling, or growth stunting. Nicosulfuron and mesotrione were found to be lethal. In contrast, quizalofop-P-ethyl, rimsulfuron, and fomesafen had phytotoxicity thresholds significantly higher than their recommended doses, indicating better crop safety. The calculated safe application intervals based on soil residue dynamics were: 67 days for fomesafen, 42 days for atrazine, and 19 days for nicosulfuron. Quizalofop-P-ethyl applied at its recommended rate caused no significant phytotoxicity. Within the tobacco-grain intercropping system, the use of mesotrione and atrazine should be strictly avoided, while acetochlor and nicosulfuron require cautious application. Optimizing the herbicide application interval based on specific herbicide characteristics is essential.