The small brown planthopper, Laodelphax striatellus, is a dangerous pest in rice fields. Although buprofezin has been used to control L. striatellus for more than a decade, the occurrence of buprofezin-resistant L. striatellus has been recently reported. To develop an alternative pest control strategy, comparative transcriptome analysis of buprofezin-treated and nontreated L. striatellus was performed to screen the buprofezin-specific target genes for RNA interference (RNAi) application. Among six genes downregulated in the buprofezin-treated L. striatellus, RNAi-based silencing of the lipophorin precursor, endocuticle structure glycoprotein, and chitin synthase significantly induced the lethality of L. striatellus in a concentration-dependent manner. In addition, a cocktail of double-stranded RNAs against these three genes showed synergistic effects with buprofezin. These results provide RNAi-based effective approaches to control L. striatellus as well as an efficient method to identify novel target genes for RNAi application.