Salinity is an important environmental factor that affects the physiological activities of fish. In order to investigate the changes of gene expression level in Nibea japonica, an economic marine fish treated by acute salinity stress, the transcriptomes of muscle tissues under different salinity conditions were sequenced based on the Illumina HiSeq^TM 2500 high-throughput sequencing platform and the data were analyzed by bioinformatics tools in this study. A total of 46 379 598 (5.27 Gb), 36 130 844 (4.87 Gb) and 38 715 820 (5.53 Gb) clean reads were obtained in the high salinity group (HS), the low salinity group (LS) and the control group (C), respectively. 91 667 transcripts were assembled and 61601 unigenes were spliced after removing redundancy. Compared with the control group, 2 230 and 1 377 differential expression genes (DEGs) were up-regulated, while 1 959 and 2 447 DEGs were down-regulated in the high salinity group and the low salinity group, respectively. Six DEGs were randomly selected for quantitative real-time PCR (qRT-PCR), and the results were consistent with the RNA-seq. 21 and 41 ion channel genes were obtained from all significant DEGs in high salinity group and low salinity group, respectively. Fourteen of 15 shared genes showed the same trend. By contrast, 6 and 10 ion transporter genes were acquired from the significant DEGs of two groups. The results of GO functional enrichment showed that the DEGs were significantly enriched in proteasome and complement activation, and KEGG pathway enrichment suggested that the DEGs were enriched in binding, catalytic activity, signal transduction and catabolism. The results indicated that the salinity adaptation of N. japonica is a complex process involving multiple tissues and genes. Besides the change of ion channels and ion transporters, the change of salinity also affects the protein degradation and immune system. The findings will provide important references for further study on the regulation mechanism of salinity adaptation and breeding of N. japonica.