ABSTRACT: The aim of the present study was to investigate the transcriptomic differences between Panax ginseng [Renshen (RS)] plants bitten by pests (n=3, test group; samples defined as RS11?13) or not (n=3, control group; samples defined as RS1?3) using de novo RNA sequencing on an Illumina HiSeq™ 2000 platform. A total of 51,097,386 (99.6%), 49,310,564 (99.5%), 59,192,372 (99.6%), 60,338,540 (99.5%), 56,976,410 (99.6%) and 54,226,588 (99.6%) clean reads were obtained for RS11, RS12, RS13, RS1, RS2 and RS3, respectively. De novo assembly generated 370,267 unigenes, 927 of which were differentially expressed genes (DEGs), including 782 significantly upregulated and 145 significantly downregulated genes. Function enrichment analysis revealed that these DEGs were located in 28 significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways, including phenylpropanoid biosynthesis (for example, TRINITY_DN30766_c0_g2_i1, encoding peroxidase 20) and mitogen?activated protein kinase (MAPK) signaling (TRINITY_DN85589_c0_g1_i1, encoding WRKY transcription factor 75). Weighted gene co?expression network analysis identified modules including TRINITY_DN85589_c0_g1_i1, TRINITY_DN58279_c0_g1_i1 [encoding aspartyl protease (AP)] and TRINITY_DN74866_c0_g2_i1 [encoding 12?oxophytodienoate reductase (OPR)] that may be the most significantly associated with pest responses. In this module, TRINITY_DN85589_c0_g1_i1 may co?express with TRINITY_DN58279_c0_g1_i1 or TRINITY_DN74866_c0_g2_i1. WRYK and AP have been suggested to promote the activity of antioxidant peroxidase. Collectively, the findings from the present study suggested that a MAPK?WRKY?OPR/AP?peroxidase signaling pathway may be a potentially important mechanism underlying defense responses against pests in ginseng plants.