Abstract: 【Objective】 To identify drought-resistance genes operating in mulberry under drought stress and reveal the molecular mechanism of drought resistance in mulberry at the transcriptional level,so as to provide a theoretical basis to support the breeding for and the selection of drought-resistance in mulberry.【Method】 The drought-sensitive mulberry variety of Deguo 1 and drought-tolerant mulberry variety Husang 32 were used as the research materials. The drought stress and the control group of rehydration treatment were carried out through pot cultivation. Total RNA was extracted from 24 mulberry leaf samples,cDNA libraries was constructed,and then subject to high-throughput sequencing on the Illumina HiSeq^TM 4000 platform. Drought-related genes were annotated and analyzed in combination with bioinformatics.【Result】 The results showed that clean reads ranged from 45723096 to 67280168,with clean bases concentrated in 6.86 Gb to 10.09 Gb,with a GC content of 44.84%-46.48%(average 45.61%)and Q30 scores of 90.36%-93.07%. The number of differentially expressed genes(DEGs)between samples(A2 vs A1,B2 vs B₁,A3 vs A1,B3 vs B₁,A4 vs A1,B4 vs B₁)were:3510, 3399, 5677, 5507, 5124 and 2734,respectively. There were a smaller number of up-regulated genes than down-regulated genes after drought stress treatment of mulberry. DEGs between the mulberries of differing drought resistance were most enriched in biological processes,consisting mainly of small molecule metabolic process,transmembrane transport and carbohydrate metabolic process. DEGs involved in molecular function were the second most enriched,consisting mainly of transferase activity and hydrolase activity. DEGs were enriched in 59 KEGG signaling pathways,which can be divided into five categories:metabolism,genetic information processing,environmental information processing, cellular processes and biological systems. Drought-resistant mulberry varieties could better adapt to drought stress by their increased expression of genes involved in energy metabolism,carbohydrate metabolism,photosynthesis and lipid metabolism. GO functional annotation and KEGG signal pathway enrichment analyses were combined to obtain the droughtresistance genes:LOC21410404,LOC21404884,LOC21409623,LOC21401352,LOC21398977,LOC21388561, LOC21401447,LOC21398764,LOC21385254,LOC21384661,LOC21410404 and LOC21408971.【Conclusion】The higher drought tolerance of the mulberry variety Husang 32 relative to the variety Deguo 1 involved significant differential expression of genes under drought stress related with enhancements in energy metabolism,carbohydrate metabolism,photosynthesis and lipid metabolism.