Ability to tolerate low salinity is a key factor affecting the distribution of the Chinese shrimp (Fenneropenaeus chinensis). Although previous studies have investigated the mechanisms underlying adaptations to low salinity in some crustaceans, little is known about low-salinity adaptations in F. chinensis, particularly at the molecular level. Here, to identify genes potentially associated with the molecular response of F. chinensis to low-salinity exposure, we compared the transcriptomes of F. chinensis in low-salinity (5 ppt) and normal-salinity (20 ppt) environments. In total, 45,297,936 and 44,685,728 clean reads were acquired from the low-salinity and control groups, respectively. De novo assembly of the clean reads yielded 159,130 unigenes, with an average length of 662.82 bp. Of these unigenes, only a small fraction (10.5% on average) were successfully annotated against six databases. We identified 3,658 differentially expressed genes (DEGs) between the low-salinity group and the control group: 1,755 DEGs were downregulated in the low-salinity group as compared to the control, and 1,903 were upregulated. Of these DEGs, 282 were significantly overrepresented in 38 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. Notably, several DEGs were associated with pathways important for osmoregulation, including the mineral absorption pathway (ATP1A, Sodium/potassium-transporting ATPase subunit alpha; CLCN2, Chloride channel 2; HMOX2, Heme oxygenase 2; SLC40A1/FPN1, Solute carrier family 40 iron-regulated transporter, member 1), the vasopressin-regulated water reabsorption pathway (AQP4, Aquaporin-4; VAMP2, Vesicle-associated membrane protein 2; RAB5, Ras-related protein Rab-5) and the ribosome pathway. Our results help to clarify the molecular basis of low-salinity adaptations in F. chinensis.