White spot syndrome virus (WSSV) is a lethal pathogen that causes 100% mortality within 3-7 days after infection. Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway play a role during WSSV infection. Previous work has shown that PmDOME and PmSTAT silencing in black tiger shrimp (Penaeus monodon ) reduced WSSV copy numbers and delayed the cumulative mortality. In this work, the next-generation sequencing (NGS) was performed using STAT-silenced shrimp, WSSV-infected STAT-silenced shrimp and WSSV-infected shrimp. Transcriptome data showed that a total of differential expression genes (DEGs) of WSSV infection was 675, while 138 up-regulated genes were from STAT-silencing + WSSV . Ten genes were randomly selected and their expression levels were verified by qRT-PCR. In addition, the roles of PmSOCS2, a JAK/STAT inhibitor, were also investigated. Silencing of PmSOCS2 significantly affected the expression of ProPO2 , ALFPm3 , Penaeidin 3 , CrustinPm1 and CrustinPm7. This work emphasizes the importance of the JAK/STAT signaling pathway during WSSV infection.