The functions of cuticular hydrocarbons (CHCs) are varied in insects, but one example is to reduce water loss. Previous work has suggested that biosynthesis of CHCs is strongly related to the CYP4G sub-family. Targeting these genes in the brown planthopper,
Nilaparvata lugens
Stål, might be a new application for integrated pest management. Therefore, we explored the functions of
CYP4G76
(GenBank: KM217045.1) and
CYP4G115
(GenBank: KM217046.1) genes in this study. The desiccation treatment (RH < 5%) for the duration of 1–3 days significantly increased the transcription level of
CYP4G76
and
CYP4G115
. RNAi through the injection of
CYP4G76
and
CYP4G115
dsRNA could significantly decrease their expression, respectively, and further reduced the biosynthesis of CHCs, i.e., saturated and straight-chain alkanes. When
CYP4G76
and
CYP4G115
were suppressed, the susceptibility of
N. lugens
nymphs to desiccation increased, due to the deficiency of the CHCs in the insect’s cuticle. When the expression of
CYP4G76
and
CYP4G115
was decreased, this resulted in an increased rate of penetration of the four insecticides: pymetrozine, imidacloprid, thiamethoxam and buprofezin. Therefore,
CYP4G76
and
CYP4G115
appear to regulate the biosynthesis of CHCs in
N. lugens
nymphs, which play a major role in protecting insects from water loss and the penetration of insecticides.
CYP4G76
and
CYP4G115
might be used as a novel target in integrated pest management to
N. lugens.