The soybean cyst nematode (SCN, Heterodera glycine Ichinohe) is a major disease affecting soybean (Glycine max (L.) Merr.) production and yield. Breeding of new SCN-resistant cultivars and understanding their resistance mechanisms are valuable for improving SCN resistance of soybean. However, we still know little about resistance mechanisms to SCN. The purpose of our analysis was to understand the different resistance mechanisms of resistant and susceptible lines to SCN by dissecting their transcriptional changes during infection by SCN HG type 1.2.3.5.7. In this study, 119 recombinant inbred lines derived from a cross of cv. Dongnong L-204 (SCN resistant) and cv. Heinong 37 (SCN susceptible) were identified for resistance status to SCN HG type 1.2.3.5.7. Roots of the lines identified as extremely resistant or susceptible (L5, L89) were sequenced by transcriptome, and we obtained 66.61 Gb of data. Compared with the untreated control, there were 8394 and 6899 differentially expressed genes in SCN-infected roots of L5 and L89, respectively. Genes of metabolic pathways, biosynthesis of secondary metabolites, plant hormone signal transduction, and plant-pathogen interaction pathway were significantly expressed in both resistant and susceptible genotypes. The expression of genes of phenylpropanoid biosynthesis, flavonoid biosynthesis, thiamine metabolism, cutin, suberin and wax biosynthesis, and endocytosis pathway was significantly higher in the resistant line than the susceptible line. Transcription factor analysis showed that 88 transcription factors from 18 transcription factor families responded to SCN stress. Nine genes were identified by reverse transcriptase qPCR to be associated with SCN resistance. This study helps us to understand better the mechanism of soybean resistance to SCN.