Abstract: Plant parasitic nematodes can directly or indirectly damage all kinds of crops in the world and cause serious economic losses. In this study, twenty-seven bis-heterocyclic ketones that have not been reported were designed and synthesized, and their lethal activity in vitro against Meloidogyne incognita and their inhibition rates in vivo caused by M. incognita in sand and matrix soil were measured. Results of the test in vitro showed that most of the compounds had no activity against M. incognita at 40 mg/L for 72 h, except for compounds D1 and E3 , which showed 70.03% and 71.26% mortality, respectively. Results of the test in vivo showed that the inhibition rates of compounds B1 , B2 , B5 , C4 , D2 , E6 and E9 in sand were higher than 90% against M. incognita at 40 mg/L, and the inhibition rate of D2 reached 87.61% at 5 mg/L, which was the highest one and higher than that of lead compound B1 . In matrix soil, the inhibitory activity of compound B5 was the strongest, and the inhibition rate was 77.67% at 40 mg/L. Preliminary analysis on the structure-activity relationship demonstrated that (5-(2-thienyl)-2-thiazolyl)-2-thienylmethanone( D2 ) without any substituents on the 2-thiophene ring had better nematicidal activity.