This study was evaluated the toxicity of three insecticides contains two effective substances, chlorpyrifos & lufenuron (Tempo XL), lufenuron & emamectin benzoate (Heater) and thiamethoxam & chlorantraniliprole (Folliam Felixi) against the 2^nd and 4^th larval instars of S. littoralis under semi-field condition in tomato field Ismailia Governorate during 2018 & 2019 seasons and assessing their biochemical effect against treated larvae. In laboratory results indicated that Heater had the highest efficacy against 2^nd  and 4^th  larval instars, with LC₅₀ of 0.041 and 0.135 ppm for 2^nd  and 4^th  larval instars, respectively, followed by Folliam Felixi with LC₅₀ of 0.076 and 0.233 ppm and finally Tempo XL with LC₅₀ of 0.097 and 0.411 ppm for 2^nd  and 4^th  larval instars, respectively. Under the semi-field condition observed that the initial effect during 2018 & 2019 seasons, Heater proved to be the most effective and had the highest corrected larval mortality, while the general mean of residual activity was more than 90% in all treatments. In biochemical studies, alpha and beta esterases were the highest activities in S. littoralis larvae treated with tested compounds compared to untreated. The highest enzyme activity of acetyl- cholinesterase, acid and alkaline phosphatase was observed in Tempo XL, while in the case of Heater and Folliam Felixi there was no significant difference between them. The results also showed that with all treatments there was a significant decrease in the total protein.