Soybean cyst nematode (SCN, Heterodera glycines Ichinohe) is a common disease of soybean (Glycine max (L.) Merr.) worldwide, seriously affecting yield. Kangxian 2 is a soybean variety with a high level of resistance to H. glycines (HG) Type 0 (SCN race 3) and a yellow seed coat. However, we know little about the mechanism of resistance to HG Type 0 in Kangxian 2. In this study, we used the Illumina HiSeq high-throughput sequencing platform to analyse the transcriptome of Kangxian 2 and obtained 65.74 Gb clean data. Transcriptional changes in Kangxian 2 caused by HG Type 0 stress after 0–10 days are described. Kangxian 2 showed different levels of gene expression after inoculation, and under HG Type 0 stress after different times. Overall, 6854 HG Type 0-induced genes and 5328 HG Type 0-repressed genes were found to be differentially regulated. The greatest number of differential genes annotated to cellular process, metabolic process, single-organism process, binding, catalytic activity and other pathways. In addition to findings of differentially expressed genes similar to other published work, such as the regulation of biosynthesis of many secondary metabolites, carbon sequestration of photosynthetic organisms, other types of O-polysaccharide biosynthesis, phenylpropane biosynthesis, pyruvate metabolism and other pathways, this study also revealed the differential regulation of genes related to the diarylheptanoid and gingerol biosynthesis pathway and found some metabolic pathways that were specifically expressed in the syncytial initiation and establishment stages. Gene expression analyses using real-time fluorescence quantitative PCR showed that the expression of GmMADS and GmTUB changed strongly after 7 days and 10 days of HG Type 0 stress compared with the control. We conclude that GmMADS and GmTUB transcription factor genes may play an important role in the resistance of Kangxian 2 to HG Type 0 stress.