Meloidogyne incognita is a major plant parasite that causes root-knot disease in numerous agricultural crops. This nematode has severely affected greenhouse crops in China. Chemical insecticides are generally used to control this pest, but they have adverse environmental and human toxicity effects; hence, safe and effective strategies for controlling the root-knot nematode (RKN) are necessary. FMRFamide-like peptides (FLPs) have diverse physiological and biological effects on the locomotory, feeding, and reproductive functions of nematodes, and mitogen-activated protein (MAP) kinase plays an important role in the regulation of transcription factors and protein kinases. These candidates are the common targets of RKN control. They are encoded by Mi-flp-18 and Mi-mpk-1 genes, respectively, in M. incognita. In this study, we used the RNA interference (RNAi) method to silence the transcription of these genes and determined the effects on the pathogenicity of RKN in potted plants. Real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) revealed that Mi-mpk-1 gene expression could be reduced by 33% by RNAi. The RNAi-treated infective nematodes were inoculated with dsRNAs of Mi-flp-18 and Mi-mpk-1 in pot experiments. The root-knot numbers were reduced by 51% after Mi-flp-18 RNAi treatment. Further, the relative abundance of Mi-flp-18 was downregulated by 79% in the endoparasitic M. incognita. Mi-flp-18 RNAi treatment decreased egg masses by 92% and egg numbers by 58%. Mi-mpk-1 RNAi treatment reduced the root-knot numbers by 32% and, remarkably, lowered the relative abundance of Mi-mpk-1 in the endoparasitic M. incognita. Egg masses and numbers were reduced by 42 and 22%, respectively, after RKN was inoculated for 35 days with Mi-mpk-1 RNAi. Therefore, Mi-flp-18 and Mi-mpk-1 genes are susceptible to RNAi and can be used as potential targets for RKN control by regulating nematode infection, parasitism, and reproduction.