Apolipoprotein D (ApoD) is a lipocalin superfamily member that plays important roles in the transport of small hydrophobic molecules, lipid metabolism, and stress resistance. Cuticular hydrocarbons are the principal components of the epicuticular lipid layer and play a critical role in water retention against environmental desiccation stress; however, the mechanism underlying the role of ApoD in insect desiccation tolerance has not yet been elucidated. Here, we report the molecular constitution, functional analysis, and phylogenetic relationship of the ApoD gene in Acyrthosiphon pisum (ApApoD). We found that ApApoD was transcribed throughout the life cycle of A. pisum, but was prominently expressed in the embryonic period and abdominal cuticle. In addition, we optimized the dose and silencing duration of RNAi, observing that RNAi against ApApoD significantly reduced the levels of both internal and cuticular hydrocarbons and adult fecundity. Moreover, cuticular hydrocarbon deficiency increased the sensitivity of aphids to desiccation stress and reduced their survival time, while desiccation stress significantly increased ApApoD expression. Together, it is confirmed that ApApoD participates in regulating cuticular hydrocarbon content of aphids under desiccation stress and is crucial for aphid reproduction. Therefore, the ApApoD gene of A. pisum may be a potential target for RNAi-based insect pest control due to its involvement in cuticular hydrocarbon accumulation and reproduction.