The black inch looper of Hyposidra talaca is one of the important defoliating pests of tea in north-eastern India which is capable of completing 6–8 generations in a year without any diapause. The looper stages of H. talaca passes through five larval instars causing considerable damage to the tea crop. The effective control of H. talaca greatly relies on application of synthetic insecticides. In the present study, we determined the relative toxicity of two selected insecticides viz., deltamethrin and quinalphos along with differential expression of the three detoxifying enzymes (general esterase, glutathione S-transferase, and cytochrome-P450-monooxygenase) in various larval stages of H. talaca populations collected from the tea ecosystem. In general, both insecticides were most active against first and second stage larvae but their toxicity levels decreased with the advancement of life stages. The expression of the three detoxifying enzymes in all five larval stages varied greatly which increased with each successive stage suggesting that these enzymes are serving as defensive mechanism for the insects to insecticidal stress. These results show that sensitivity of insecticides was directly related to the stage of the insect and suggests that chemical treatment at early stages of the insect is more effective than at later stages. Results of the present work reveal the mechanisms underlying in the adaptation of H. talaca to insecticides which would be of considerable significance for the development of effective pest management strategies.