In this study, 1, 5, and 10 mg/g ferulic acid were added to the diet of the Spodoptera frugiperda (S. frugiperda) to observe their effects on the larval duration, larval body length, body mass, pupation rate, and emergence rate. Transcriptome sequencing combined with RNA interference was used to investigate the detoxification function of detoxification metabolic enzymes in the S. frugiperda against ferulic acid. The results showed that, compared with the acetone-fed control, the developmental period of larvae treated with 10 mg/g ferulic acid was extended by 1.6 times; the pupal mass was only 34% of the control; and the pupation and eclosion rates were reduced by 80.4% and 77.7%, respectively. Ferulic acid treatment activated the expression of multiple detoxification metabolic enzyme genes in the S. frugiperda, and silencing of detoxification enzymes SfCYP6B6 and SfUGT2B15 could significantly enhance the lethal effect of ferulic acid on the S. frugiperda. Compared with the acetone-fed control, the 72 h lethality rate of ferulic acid on larvae with silenced SfCYP6B6 and SfUGT2B15 increased by 36.7% and 52.6%, respectively.