| In order to investigate the variations of gene expression of salivary gland in Hirudo nipponia under starvation stress, two libraries of starvation treatment group (D30) and control group(D0) were constructed and sequenced using the Illumina HiSeq 2500 platform (paired-end). After stringent quality control of raw data, 145981 unigenes were obtained using de novo assembly. The average length of unigenes was 675 bp and N50 lengths was 1127 bp. And then all of unigenes were annotated via sequence alignment analysis in CDD, KOG, COG, NR, NT, PFAM, Swissprot, TrEMBL, GO and KEGG databases. The amount of gene expression was also estimated according to TPM (Transcripts Per Kilobase Million). By comparing the transcriptome data of D30 sample and D0 sample, the differentially expressed genes (DEGs) were screened out with a threshold criteria Q Value<0.05 and |FoldChange|> 2. Totally 2650 DEGs were identified under starvation stress, among which 667 genes were up-regulated and 1983 genes were down-regulated. Four functional DEGs were selected for RT-qPCR analysis, and the results confirmed that the transcriptome analysis was reliable. In addition, 175 pathways were significantly enriched when the DEGs were subject to GO enrichment analysis. The results showed that most of the DEGs were involved in cytoplasmic ribosome pathway and ribosome pathway. The DEGs were almost down-regulated in these pathways. It also was proved in KEGG enrichment analysis that most DEGs were involved in ribosome pathway. The DEGs down-regulated in ribosome pathway can indicate that it reduces protein metabolism under starvation stress. Futhermore, were predicted to be involved in anticoagulatory, antithrombotic, antibacterial, anti-inflammatory and antitumor processes, which might play important roles in the treatment of various diseases. The results above mentioned provide foundation information for further study on the molecular mechanism of starvation tolerance of salivary gland and the discovery of pharmaceutical value genes in Hirudo nipponia, and also provides reference for other medicinal leeches.