In order to analyze the variation of differentially expressed genes and the regulation mechanism of “drywet” adaptation in N. flagelliforme under hydration and dehydration. Highthroughput Illumina HiSeq PE150 sequencing platform and bioinformatics method were used to screen the droughttolerant differentially expressed genes of N. flagelliforme in this study. The results showed that: (1) a total of 3 383 differentially expressed genes were identified under hydration and dehydration, among which the significantly upregulated and downregulated genes were 1 767 and 1 616, respectively. (2) GO function enrichment analysis showed that the expression and regulation of differentially expressed genes mainly focused on protein synthesis and metabolism pathway in N. flagelliforme under dehydration. The KEGG significant enrichment analysis showed that the 46 differentially expressed genes in N. flagelliforme under hydration and dehydration were significantly enriched to the ribosomal metabolic pathway, all of which were upregulated. (3) Six genes that were significantly enriched in the ribosomal metabolic pathway were randomly selected for qRTPCR analysis, and the gene expression levels were consistent with the transcriptome sequencing results. These results suggested that N. flagelliforme might adapt to drought stress by inducing the gene expressions of ribosomal metabolic pathway in order to promoting droughtrelated protein synthesis and correct folding. These proteins involved in osmotic regulation and other important physiological activities in N. flagelliforme under dehydration.