The cotton–melon aphid (Aphis gossypii Glover), a globally distributed polyphagous pest, primarily infests cucurbit crops and leads to significant reductions in both crop yield and quality. Overreliance on chemical insecticides has resulted in widespread resistance development, highlighting the urgent requirement for alternative control strategies. This study evaluates the potential of topical RNA interference (RNAi) for managing cotton–melon aphids. We first analyzed instar-specific expression profiles of four candidate RNAi target genes (ATPE, IAP, Cat, and ilvE), employed topical dsRNA delivery to silence these genes, and subsequently evaluated their effects on aphid mortality, growth rates, and reproductive capacity. Furthermore, we investigated the non-target effects of RNAi-treated aphids on the predator ladybird beetles Propylea japonica. The results indicate that topical dsRNA delivery successfully silenced the target genes, significantly impairing aphid development and fecundity while inducing mortality, with no adverse effects on the beneficial predator. This method provides a powerful tool for insect gene functional studies and a promising solution for RNAi-based pest management.