Lipophilic metabolites play important role in the developmental process of insects, however, still there is no clarity on their involvement in plant resistance. Therefore, we carried out the lipophilic profile of host sorghum genotype seedlings and the Chilo partellus (Swinhoe) larvae, to understand the role and contribution of certain lipophilic metabolites in sorghum plant defense against the dreaded pest, spotted stem borer, C. partellus . There were variations in the form of presence or absence, along with significant differences in lipophilic metabolites across sorghum genotypes and the C. partellus larvae. The significantly higher contents of myristic acid, palmitic acid, linoleic acid, linolenic acid, eicosanoic acid and behenic acid in resistant sorghum genotypes; and linolenic acid, methyl 3-methoxytetradecanoate, myristic acid, oleic acid, palmitic acid, palmitoleic acid, lathosterol and squalene in C. partellus larvae were significantly lower than those fed on susceptible genotype, indicating their role in insect-plant biochemical disruptions. Myristic acid, methyl 3-methoxy-tetradecanoate, stearic acid, squalene, fucosterol, hexacontane, tetrapentacontane, palmitic acid, l-(+)-ascorbic acid 2,6-dihexa-decanoate, 2-pentadecanone, 6,10,14-trimethyl, lignoceric acid and stigmasterol in sorghum seedlings contributed to 60 to 100% variability in various biological and resistance parameters of C. partellus . However, myristic acid, linoleic acid, margaric acid, methyl 14-methylhexadecanoate, methyl 3-methoxytetradecanoate, stearic acid, palmitic acid, palmitoleic acid, eicosanoic acid, gamma-ergostenol, cholesterol, lathosterol, squalene, 1-triacontanol and n-pentadecanol in C. partellus larvae contributed to 64 to 100% variability in various biological and resistance parameters of C. partellus . The myristic acid, methyl 3-methoxytetradecanoate, palmitic acid, stearic acid and squalene present in both host plant and the test insect, contributed significantly to explain variability in resistance against C. partellus , thus could be used as biomarkers for sorghum-stem borer interactions.