The novel difluoromethylpyrazole derivatives containing flexible alkyl chain moieties were designed and synthesized. Compound 6-9 and 6-23 possessed most good nematocidal activity against M. incognita with low toxicity. Compound 6-9 also exhibited low toxicity against rat and no eye or skin sensitization against rabbit. Molecular docking study suggested that the flexible NHCOO group of compound 6-9 inhibited the acetylcholine receptor (AChR).