BACKGROUNDTo improve integrated pest management (IPM) performance it is essential to assess pesticide side effects on host plants, insect pests, and natural enemies. The green peach aphid (Myzus persicae Sulzer) is a major insect pest that attacks various crops. Aphidius gifuensis is an essential natural enemy of M. persicae that has been applied effectively in controlling M. persicae. Thiamethoxam is a neonicotinoid pesticide widely used against insect pests.RESULTSThe current study showed the effect of thiamethoxam against S. tuberosum, M. persicae, and A. gefiuensis and the physiological and molecular response of the plants, aphids, and parasitoids after thiamethoxam application. Thiamethoxam affected the physical parameters of S. tuberosum and generated a variety of sublethal effects on M. persicae and A. gefiuensis, including nymph development time, adult longevity, and fertility. Our results showed that different thiamethoxam concentrations (0.1, 0.5, and 0.9 μm a.i/L) on different time durations (2, 6, and 10 days) increased the antioxidant enzyme activities SOD, POD, and CAT of S. tuberosum, M. persicae, and A. gefiuensis significantly compared to the control. Our results also showed that different thiamethoxam concentrations (0.1, 0.5, and 0.9 μm a.i/L) on different time durations (2, 6, and 10 days) increased the expression of SOD, POD, CAT, AChE, CaRE, and GST genes of S. tuberosum, M. persicae, and A. gefiuensis compared to the control.CONCLUSIONOur findings reveal that using thiamethoxam at suitable concentrations and time durations for host plants and natural enemies may enhance natural control through the conservation of natural enemies by overcoming any fitness disadvantages.This article is protected by copyright. All rights reserved.