Abstract: To effectively control plant viral diseases caused by tomato spotted wilt virus (TSWV), antiviral lead compounds were extracted from plants. Lesion counting was used to detect the activities of TSWV after treating with 14 sesquiterpenoids from Tithonia diversifolia. The results showed that applying 14 sesquiterpenoids (100 μg/mL) after inoculation with virus for 24 h, the inhibition rates of seven sesquiterpenoids were higher than Ningnanmycin (CK, 58.80%) in control experiment. The inhibition rate of sesquiterpenoids-12 was the highest (76.00%). Inoculated with virus after applying 14 sesquiterpenoids for 6 h, the inhibition rates of four sesquiterpenoids were higher than Ningnanmycin (61.25%), and the inhibition rate of sesquiterpenoids-12 was 78.50%. Inhibition rate of sesquiterpenoids increased with the rising of concentration, which showed a concentration-dependent manner. In control and protection experiments, when the concentration was 200 μg/mL, the inhibition rates of sesquiterpenoids-12 were 86.00% and 89.20%, respectively. Therefore, sesquiterpenoids from Tithonia diversifolia could be used as lead compounds of biopesticides in resistance to TSWV.