Protoporphyrinogen oxidase (PPO) is an important target for discovering new herbicides that interfere with the synthesis of porphyrin. In order to discover new PPO inhibitor herbicides with improved biological activity, a series of new diphenyl ethers containing tetrahydrophthalimide are designed and synthesized. Among them, J6.1 (IC50=4.7 nM) and J6.3 (IC50=30.0 nM) show higher maize (Zea mays L.)PPO inhibitory activity than the commercial herbicides, i.e., oxyfluorfen (IC50=117.9 nM) and flumioxazin (IC50=157.1 nM). The greenhouse herbicidal activity of J6.3 is comparable to that of oxyfluorfen, and it is greater than that of flumioxazin. Even at a dose of 300 g active ingredients/hectare (a.i/ha), cotton (Gossypium hirsutum L.) and peanut (Arachis hypogaea L.) show greater tolerance to J6.3, suggesting that J6.3 could be used for further development of new herbicide candidates in those fields. In addition, molecular docking has been used to further study its mechanism of action. The results show that the introduction of nitro group and tetrahydrophthalimide into the diphenyl ether structure is beneficial to biological activity.