System level knowledge of host alterations is crucial to elucidate the molecular events of viral pathogenesis and to develop strategies to block viral establishment and amplification. Here, we applied quantitative proteomics approach to study global proteome changes in the host; Spodoptera frugiperda upon infection by a baculovirus, Spodoptera litura NPV at two stages i.e. 12h and 72h post infection. At 12hpi, >95% of host proteins remained stable, however at 72hpi, 52% host proteins exhibited downregulation of 2-fold or more. Functional analysis revealed significant upregulation of transposition and proteasomal machinery while translation, transcription, protein export and oxidative phosphorylation pathways were adversely affected. An assessment of perturbed proteome after viral infection and viral miRNAs expression led to the identification of 117 genes that are potential targets of 10 viral miRNAs. Using miRNA mimics, we confirmed the down regulation of 9 host genes. The results comprehensively show dynamics of host responses after viral infection.