The codling moth, Cydia pomonella (L.), is a key worldwide fruit pest that has evolved high levels of resistance to almost all classes of conventional insecticides. Neonicotinoids, a new reduced-risk biorational insecticide class, have remained an effective control approach. In this study, the toxicity and sublethal effect of conventional and reduced-risk biorational insecticides on transcripts abundance of three detoxification genes in codling moth were determined. Bioassays on a codling moth laboratory strain suggested that acetamiprid had the highest oral toxicity against the third-instar larvae compared with the other five pesticides. Results also indicated that acetamiprid exhibits long-Term efficacy against codling moth even at 120 h post feeding. Real-Time quantitative polymerase chain reaction showed that the detoxification genes CYP9A61, CpGST1, and CpCE-1 were differentially induced or suppressed by deltamethrin, cypermethrin, methomyl, carbaryl, and imidacloprid, depending on the type of insecticides; in contrast, no significant difference in CYP9A61, CpGST1, and CpCE-1 expressions were observed after acetamiprid exposure, when compared with the control. These results suggest that the reduced-risk biorational insecticide acetamiprid is an effective insecticide with no induction of detoxification genes and can be integrated into the management of codling moth.