RNA interference (RNAi) techniques have emerged as powerful tools that facilitate development of novel management strategies for insect pests, such as Henosepilachna vigintioctopunctata (Coleoptera: Coccinellidae), which is a major pest of solanaceous plants in Asia. In this study, the potential of oral delivery of in vitro-synthesized and bacterially expressed double-stranded H. vigintioctopunctata lesswright (lwr) gene (dsHvlwr) to manage of H. vigintioctopunctata was investigated. Our results showed that the gene Hvlwr had a 480-bp open reading frame and encoded a 160-amino acid protein. Hvlwr expression levels were greater in the fat body than other tissue types. Hvlwr silencing led to greater H. vigintioctopunctata mortality rates and appeared to be time- and partially dose-dependent, likely as a result of the number of hemocytes increasing with dsRNA concentration, but decreasing with time. Bacterially expressed dsHvlwr that was applied to leaf discs caused 88%, 66%, and 36% mortality in 1st instars, 3rd instars, and adults after 10, 10, and 14 d, respectively; when applied to living plants, there was greater mortality in 1st and 3rd instars, but there was no effect on adults. Furthermore, dsHvlwr led to improved plant protection against H. vigintioctopunctata. Our study shows an effective dietary RNAi response in H. vigintioctopunctata and that Hvlwr is a promising RNAi target gene for control of this pest species.