Abstract We investigated the effectiveness and biochemical impact of the insecticides flubendiamide and flonicamid compared with azadirachtin and acetamiprid against the whitefly Bemisia tabaci (Grennadius) (Hemiptera: Aleyrodidae) infesting cherry tomato (Solanum lycopersicum var. cerasiforme L.) grown under greenhouse conditions. The dissipation of both insecticides in the plants and in the soil also was determined using the QuEChERS (quick, easy, cheap, effective, rugged, and safe) and liquid chromatography–electrospray ionization–mass spectrometry methods. Both insecticides were more effective for reducing B. tabaci populations than were either acetamiprid or azadirachtin. Biochemical analysis revealed that esterase may play an important role in whitefly adaptation to flubendiamide and flonicamid. The QuEChERS method was determined suitable for quickly detecting residues of flubendiamide and flonicamid in complex matrices. The recovery rates on tomato fruit samples were 92.8–106.0%, with a relative standard deviation (RSD) range of 0.46–2.65%. For soil samples, the recovery rates were 81.3–95.7% with RSDs of 1.20–3.86%. We further determined that flubendiamide had dissipation half-lives of 3.13, 3.63, and 3.68 d in tomato fruit, tomato leaves, and soil, respectively. Flonicamid had half-lives of 4.25, 3.54, and 2.60 d in fruit, leaves, and soil, respectively. These results suggest that preharvest intervals of 3 and 7 d are appropriate for flubendiamide and flonicamid, respectively, in cherry tomato production. The risk quotient was >1 by the day 5 after application; however, that value declined to <1 on day 7 after application, indicating little long-term risk to human health.